A traditional Chinese medicine composition for treating post-acute myocardial infarction depression

Abstract

This invention discloses a traditional Chinese medicine composition for treating post-acute myocardial infarction (AMI) depression, belonging to the field of traditional Chinese medicine technology. The key technical points are: it is composed of 30g of raw Astragalus membranaceus, 10g of Cyperus rotundus, 20g of Ligusticum chuanxiong, 10g of Coptis chinensis, and 10g of Bupleurum chinense. This invention can treat post-AMI depression by intervening in key inflammatory biomarker targets TNF-α, AKT, IL-1β, IL-6, and PTGS2.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and more specifically, to a traditional Chinese medicine composition for treating depression following acute myocardial infarction. Background Technology

[0002] Acute myocardial infarction (AMI) has high rates of disability and mortality, imposing a huge economic burden on society and families. Previous studies have shown that depression is one of the most common mood disorders following AMI, with an incidence rate as high as 20%-40%, far exceeding that of the general population (5%-10%). This prospective clinical study found that depression can affect the incidence of malignant arrhythmias and cardiogenic shock (MACE) in AMI patients, and is an independent predictor of MACE in AMI patients. Moreover, the more severe the depression after AMI, the higher the incidence of MACE. Previous studies have also found that depression is an independent risk factor for poor prognosis of cardiovascular diseases such as coronary artery disease and acute coronary syndrome, seriously affecting patients' quality of life.

[0003] Currently, the treatment for post-acute myocardial infarction (AMI) depression mainly involves basic medication combined with antidepressants such as SSRIs. However, this treatment method has limitations such as poor patient compliance and numerous side effects. Traditional Chinese medicine, through its approach of "treating both the heart and mind," can circumvent the risks associated with the above treatment regimens. Therefore, the inventors propose a traditional Chinese medicine composition for treating post-acute myocardial infarction (AMI) depression. Summary of the Invention

[0004] The purpose of this invention is to provide a traditional Chinese medicine composition for treating post-acute myocardial infarction depression, thereby solving the above-mentioned problems.

[0005] The above-mentioned technical objective of this invention is achieved through the following technical solution: a traditional Chinese medicine composition for treating depression after acute myocardial infarction (AMI), comprising 30 g of raw Astragalus membranaceus, 10 g of Cyperus rotundus, 20 g of Ligusticum chuanxiong, 10 g of Coptis chinensis, and 10 g of Bupleurum chinense. This invention defines this traditional Chinese medicine composition as a formula for benefiting the heart and relieving depression.

[0006] The Yixin Jieyu Formula consists of five Chinese herbs: Astragalus membranaceus, Cyperus rotundus, Ligusticum chuanxiong, Coptis chinensis, and Bupleurum chinense. The formula is refined and has shown good clinical efficacy. Astragalus membranaceus and Cyperus rotundus are the principal herbs, Ligusticum chuanxiong is the assistant herb, Coptis chinensis is the adjuvant herb, and Bupleurum chinense is the guiding herb. The combination of these herbs invigorates qi, promotes blood circulation, and relieves depression, effectively treating post-AMI (Acute Myocardial Infarction) depression.

[0007] The present invention is further configured such that the traditional Chinese medicine composition is in the form of granules or decoction.

[0008] The present invention is further configured such that the traditional Chinese medicine composition treats post-acute myocardial infarction (AMI) depression by inhibiting the inflammatory response.

[0009] In summary, the present invention has the following beneficial effects: Yixin Jieyu Formula can improve cardiac function and depressive-like behavior in rats with depression after AMI, and reduce myocardial cell morphological damage, inflammatory cell infiltration and myocardial fibrosis; Yixin Jieyu Formula can simultaneously regulate key inflammatory biomarker targets TNF-α, AKT, IL-1β, IL-6 and PTGS2 in the heart and hippocampus, exert anti-inflammatory effects, and treat depression after AMI. Attached Figure Description

[0010] Figure 1 It is a key target of traditional Chinese medicine pharmacological regulation network; Figure 2 These are representative echocardiograms of rats from each group; Figure 3 This is a comparison of LVEF and LVFS in the hearts of rats in each group (Note: compared with the sham-operated group, ** P < 0.01; compared with the model group, # P < 0.05, ## P < 0.01; compared with the AMI group alone, △ P < 0.05, △△ (P < 0.01) Figure 4 This is a comparison of LVIDs and LVIDd in the hearts of rats in each group (Note: compared with the sham-operated group, ** P < 0.01; compared with the model group, # P < 0.05, ## P < 0.01; compared with the AMI group alone, △△ (P < 0.01) Figure 5 The results of HE staining of the marginal zone of myocardial infarction in rats in each group (×400) are shown. Figure 6 Masson staining results of the marginal zone of myocardial infarction in rats of each group (×400); Figure 7 The ratio of CVF in the border zone of myocardial infarction in each group of rats (Note: compared with the sham-operated group, ** P < 0.01; compared with the model group, ## P < 0.01; compared with the simple AMI group, △△ P < 0.01. Figure 8 This is a comparison of the open field test scores of rats in different groups after myocardial infarction modeling and before depression modeling. Figure 9 This is a comparison of the open field test scores of rats in different groups after 28 days of depression modeling; Figure 10 This is a comparison of the open field test scores of rats in each group 14 days after drug intervention (Note: compared with the model group, ## P <0.01; compared with the positive drug control group, && P < 0.01; compared with the high-dose group of Yixin Jieyu Fang, ◇◇ (P < 0.01) Figure 11 This study compares the sucrose preference test among different groups of rats after myocardial infarction modeling and before depression modeling. Figure 12 This is a comparison of sucrose preference test results among rats in different groups after 28 days of depression modeling (Note: compared with the sham-operated group). ** P <0.01; compared with the model group, ## P < 0.01); Figure 13 Comparison of sucrose preference test among rats in different groups after 14 days of drug intervention; Figure 14 This is a comparison of the body weight of rats in different groups after myocardial infarction modeling and before depression modeling; Figure 15 This is a comparison of the body weight of rats in different groups after 28 days of depression modeling; Figure 16 This is a comparison of the body weight of rats in each group after 14 days of drug intervention; Figure 17 This is a comparison of the 5-HT content in the hippocampus of rats in each group (Note: compared with the sham-operated group: ** P < 0.01; Compared with the model group: # P < 0.05, ## (P < 0.01) Figure 18 The effect of Yixin Jieyu Formula on the expression of inflammatory biomarkers TNF-α, IL-6, IL-1β, AKT, and PTGS2 mRNA in the marginal zone of myocardial infarction and hippocampus of depressed rats after acute myocardial infarction (Note: compared with the sham-operated group, ** P < 0.01; compared with the model group, # P < 0.05, ## P < 0.01. (a), (c), (e), (g), and (i) represent the mRNA expression of TNF-α, IL-6, IL-1β, AKT, and PTGS2 in the borderline region of myocardial infarction; (b), (d), (f), (h), and (j) represent the mRNA expression of TNF-α, IL-6, IL-1β, AKT, and PTGS2 in the hippocampus. Figure 19Western blot analysis was used to detect the expression of TNF-α, IL-6, IL-1β, AKT, and PTGS2 proteins in the myocardial infarction border zone of rats in each group. Figure 20 Western blot analysis was used to detect the expression of TNF-α, IL-6, IL-1β, AKT, and PTGS2 proteins in the hippocampus of rats in each group. Figure 21 The effects of Yixin Jieyu Formula on the expression of TNF-α, IL-6, IL-1β, AKT, and PTGS2 proteins in the myocardial infarction border zone and hippocampus of depressed rats after acute myocardial infarction (Note: compared with the sham-operated group, ** P < 0.01; compared with the model group, # P < 0.05, ## P < 0.01, (a), (c), (e), (g), (i) represent the protein expression levels of TNF-α, IL-6, IL-1β, AKT, and PTGS2 in the myocardial infarction border region; (b), (d), (f), (h), (j) represent the protein expression levels of TNF-α, IL-6, IL-1β, AKT, and PTGS2 in the hippocampus. Detailed Implementation

[0011] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0012] Example: A traditional Chinese medicine composition for treating depression following acute myocardial infarction (AMI) consists of 30 g of raw Astragalus membranaceus, 10 g of Cyperus rotundus, 20 g of Ligusticum chuanxiong, 10 g of Coptis chinensis, and 10 g of Bupleurum chinense.

[0013] In this embodiment, the traditional Chinese medicine composition is in the form of granules or decoction.

[0014] Network pharmacology prediction validation 1. Venn diagram By consulting the TCMSP database and searching literature, the number of active ingredients in the five traditional Chinese medicines of Yixin Jieyu Formula was identified. Based on the TCMSP, Pubchem, Swiss Target Prediction, and STITCH databases, 237 potential drug targets corresponding to 53 active ingredients were obtained. Using the Genecards, OMIM, DisGeNET, and Malacards databases, 1161 related targets for AMI and 289 related targets for depression were found. The intersection of AMI and depression prediction targets yielded 91 disease intersection targets. A Venn diagram was constructed, identifying 33 candidate key target genes for Yixin Jieyu Formula in treating AMI and depression, such as... Figure 1 As shown.

[0015] 2. PPI Network Construction The key target genes were imported into the STRING software to construct a PPI network. After removing discrete proteins, the network contained a total of 229 protein-protein interaction pairs.

[0016] KEGG enrichment analysis revealed that key target genes were significantly enriched in 210 pathways, including the AGE-RAGE signaling pathway, fluid shear stress and atherosclerosis, and the IL-17 signaling pathway.

[0017] 3. Key Target-Function-Pathway Regulatory Network Key Target Pharmacological Regulation Network of Traditional Chinese Medicine Active ingredients corresponding to key targets were extracted, and a pharmacological regulatory network of traditional Chinese medicine was constructed, comprising 5 herbs from the Yixin Jieyu formula, representing 2 diseases (AMI and depression), 33 key targets, and 41 active ingredients. Results are as follows: Figure 1 As shown.

[0018] 4. Molecular docking Five key target genes (TNF, IL-6, IL-1β, AKT1, and PTGS2) with the highest connectivity in the PPI network were selected as receptors and molecular docking was performed with the corresponding active ingredients with the highest OB values ​​in the Yixin Jieyu formula. The molecular docking binding energies and their PDBIDs are shown in Table 1.

[0019] Table 1 Molecular docking binding energy

[0020] In summary, this study, through network pharmacology and molecular docking, found that Yixin Jieyu Formula treats post-AMI depression by intervening in key inflammatory biomarker targets TNF-α, AKT, IL-1β, IL-6, and PTGS2.

[0021] Experimental Case (Effects and Mechanisms of AMI in Depressed Rats) 1.1 Laboratory Animals Healthy male Sprague Dawley (SD) rats, weighing (200 ± 20) g, 8 weeks old, SPF (Specific pathogen free) grade, were provided by Beijing Huafukang Biotechnology Co., Ltd.

[0022] 1.2 Experimental Drugs Traditional Chinese medicine: Yixin Jieyu granules (raw Astragalus membranaceus 30 g, Cyperus rotundus 10 g, Ligusticum chuanxiong 20 g, Coptis chinensis 10 g, Bupleurum chinense 10 g), provided by Jiangyin Tianjiang Pharmaceutical Co., Ltd.; Anesthetic drugs: sodium pentobarbital provided by Merck GmbH, Germany; isoflurane (100 ml / vial) provided by Hebei Jindafu Pharmaceutical Co., Ltd.; sodium penicillin for injection (800,000 units / vial) provided by North China Pharmaceutical Co., Ltd.

[0023] 2 Experimental Methods 2.1 Model Preparation (1) AMI model An AMI rat model was established using the conventional method of ligating the left anterior descending coronary artery.

[0024] (2) Sham surgery model The sham surgical model is prepared by threading the sutures but not ligating them; the remaining steps are the same as those for the AMI model.

[0025] (3) Depression model A rat depression model was established by using chronic, unpredictable, mild stimulation combined with isolation.

[0026] (4) Post-AMI depression model After 7 days of acclimatization, experimental rats were induced to develop acute myocardial infarction (AMI). Three days after the AMI model was confirmed by electrocardiogram and echocardiogram, a 28-day depression model was established. Behavioral tests were used to evaluate the depressive state of the rats, and the rats that were successfully induced to develop depression were identified as the AMI post-depression model.

[0027] 2.2 Grouping and Intervention Methods The experimental rats were randomly divided into 8 groups using a random number table: sham operation group, simple AMI group, simple depression group, post-AMI depression group (model group), positive control group, high-dose Yixin Jieyu Fang group (YXJYF-H), medium-dose Yixin Jieyu Fang group (YXJYF-M), and low-dose Yixin Jieyu Fang group (YXJYF-L), with 16 rats in each group.

[0028] Starting the day after the successful establishment of the depression model following AMI, the eight groups of rats were administered the following doses by gavage once every morning at the same time (for 14 consecutive days). The specific intervention methods are shown in Table 2.

[0029] Table 2 Grouping and Intervention Methods

[0030] 2.3 Experimental Materials After the last administration, echocardiography and behavioral tests such as OFT and sucrose preference tests were performed on rats in each group. Before sampling, rats were randomly divided into perfusion group and meristem group, weighed sequentially, and then abdominal aortic blood, heart, and brain were collected sequentially.

[0031] 3. Experimental Results 3.1 Rat survival status Before sampling, the survival rates of rats in each group were as follows: In the sham-operated group, 2 rats died and 14 survived (87.50%); in the simple AMI group, 4 rats died and 12 survived (75.00%); in the simple depression group, 2 rats died and 14 survived (87.50%); in the model group, 6 rats died and 10 survived (62.50%); in the positive drug control group, 5 rats died and 11 survived (68.75%); in the high-dose Yixin Jieyu Fang group, 4 rats died and 12 survived (75.00%); in the medium-dose Yixin Jieyu Fang group, 5 rats died and 11 survived (68.75%); and in the low-dose Yixin Jieyu Fang group, 6 rats died and 10 survived (62.50%).

[0032] 3.2 Effects of Yixin Jieyu Formula on Cardiac Structure and Function in Rats with Depression After AMI 3.2.1 Echocardiography Representative echocardiograms of rats from each group are shown below. Figure 2 As shown.

[0033] (1) Left ventricular ejection fraction and left ventricular fractional shortening 1) Left ventricular ejection fraction (LVEF) Compared with the sham-operated group, the LVEF of rats in the simple AMI group and the model group was significantly decreased (P < 0.01), while there was no significant difference in LVEF in the simple depression group (P > 0.05). Compared with the simple AMI group, the LVEF of rats in the simple depression group was significantly increased (P < 0.01), while the LVEF of rats in the model group was significantly decreased (P < 0.05). Compared with the model group, the LVEF of rats in the simple depression group, the positive drug control group, and the high, medium, and low dose groups of Yixin Jieyu Fang were all significantly increased (P < 0.05). These results indicate that depression can further reduce the LVEF of rats with AMI, while Yixin Jieyu Fang can significantly increase the LVEF of rats with depression after AMI. However, there was no significant difference in LVEF among the positive drug control group and the high, medium, and low dose groups of Yixin Jieyu Fang (P > 0.05). Figure 3 (a).

[0034] 2) Left ventricular fractional shortening (LVFS) Compared with the sham-operated group, the LVFS of rats in the simple AMI group and the model group was significantly decreased (P < 0.01), but there was no significant difference in LVFS in the simple depression group (P > 0.05). Compared with the simple AMI group, the LVFS of rats in the simple depression group was significantly increased (P < 0.01), while there was no significant difference in LVFS in the model group (P > 0.05). Compared with the model group, the LVFS of rats in the simple depression group, the positive drug control group, and the high-dose Yixin Jieyu Fang group were all significantly increased (P < 0.01), while there was no significant difference in LVFS between the medium- and low-dose Yixin Jieyu Fang groups (P > 0.05). These results suggest that although the LVFS of rats in the depression group after AMI was not significantly lower than that in the simple AMI group, there was still a decreasing trend, while Yixin Jieyu Fang could significantly improve the LVFS of rats in depression after AMI. Furthermore, there was no significant difference in LVFS between the positive drug control group and the high-dose Yixin Jieyu Fang group (P > 0.05). See Figure 3 (b).

[0035] (2) Left ventricular end-diastolic diameter and left ventricular end-systolic diameter 1) Left ventricular end-systolic diameters (LVIDs) Compared with the sham-operated group, the LVIDs of rats in the simple AMI group and the model group were significantly increased (P < 0.01), while there was no significant difference in LVIDs in the simple depression group (P > 0.05). Compared with the simple AMI group, the LVIDs of rats in the simple depression group were significantly decreased (P < 0.01), while there was no significant difference in LVIDs in the model group (P > 0.05). Compared with the model group, the LVIDs of rats in the simple depression group were significantly decreased (P < 0.01), but there were no significant differences in LVIDs in the positive control group, and in the high, medium, and low dose groups of Yixin Jieyu Fang (P > 0.05). See Figure 4 (a).

[0036] 2) Left ventricular end-diastolic diameter (LVIDd) Compared with the sham-operated group, the LVIDd of rats in the simple AMI group and the model group was significantly increased (P < 0.01), while there was no significant difference in LVIDd in the simple depression group (P > 0.05). Compared with the simple AMI group, the LVIDd of rats in the simple depression group was significantly decreased (P < 0.01), while there was no significant difference in LVIDd in the model group (P > 0.05). Compared with the model group, the LVIDd of rats in the simple depression group and the positive drug control group was significantly decreased (P < 0.05), but there was no statistically significant difference in LVIDd between the high, medium, and low dose groups of Yixin Jieyu Fang and the model group (P > 0.05). See Figure 4 (b).

[0037] 3.2.2 HE staining of cardiac tissue HE staining of the marginal zone of myocardial infarction in rats showed that depression could further aggravate cardiomyocyte morphological damage and inflammatory cell infiltration in AMI rats, while Yixin Jieyu Decoction could alleviate cardiomyocyte morphological damage in depressed rats after AMI, with higher doses showing better effects. (See...) Figure 5 .

[0038] 3.2.3 Masson staining and collagen volume fraction of cardiac tissue (1) Masson staining In the sham-operated group, the myocardial fibers of rats were arranged in an orderly manner, and no obvious blue collagen fibers were observed in the intercellular matrix. In the simple depression group, the myocardial fibers were mildly disordered, and no large amounts of blue collagen deposition were observed. Compared with the sham-operated group, the simple AMI group showed disordered myocardial fiber arrangement, increased intercellular blue collagen fibers, and significant myocardial fibrosis. The model group showed more severe disordered myocardial fiber arrangement, more blue collagen fiber deposition, and a higher degree of fibrosis compared to the simple AMI group. Compared with the model group, the positive control group and all doses of the Yixin Jieyu formula showed varying degrees of reduction in blue myocardial collagen fiber deposition, reduced disordered myocardial fiber arrangement, and improved fibrosis. Figure 6 .

[0039] (2) Collagen volume fraction (CVF) Compared with sham surgery, CVF was significantly increased in the simple AMI group and the model group (P < 0.01), while there was no significant difference in CVF in the simple depression group (P > 0.05). Compared with the simple AMI group, CVF was significantly decreased in the simple depression group (P < 0.01), while CVF was significantly increased in the model group (P < 0.01). Compared with the model group, CVF was significantly decreased in the simple depression group, the positive drug control group, and the high, medium, and low dose groups of Yixin Jieyu Fang (P < 0.01). Compared with the positive drug control group, CVF was significantly decreased in the high dose group of Yixin Jieyu Fang (P < 0.01), while there was no significant difference in the medium dose group (P > 0.05). Compared with the high dose group of Yixin Jieyu Fang, CVF was significantly increased in both the medium and low dose groups (P < 0.01). See Figure 7 .

[0040] 3.3 Effects of Yixin Jieyu Formula on Depressive-like Behavior in Rats with AMI 3.3.1 Open Field Test (1) Open field test of rats in each group after myocardial infarction modeling and before depression modeling Statistical analysis revealed no significant differences in open field test scores and vertical movement scores among the rat groups after myocardial infarction modeling and before depression modeling (P > 0.05). This indicates that the open field test scores of rats after behavioral screening and randomization were comparable across groups. See [link to article / document]. Figure 8 .

[0041] (2) Open field test of rats in each group after 28 days of depression modeling Compared with the sham-operated group, the horizontal and vertical motor scores of rats in the simple AMI group, simple depression group, and model group were significantly decreased (P < 0.01); compared with the simple AMI group, the horizontal and vertical motor scores of rats in the simple depression group were significantly decreased (P < 0.01); compared with the model group, the horizontal and vertical motor scores of rats in the simple AMI group and simple depression group were significantly increased (P < 0.01); there were no significant differences in horizontal and vertical motor scores among the model group, positive drug control group, and high, medium, and low dose groups of Yixin Jieyu Fang (P > 0.05). Figure 9 .

[0042] (3) Open field test of rats in each group 14 days after drug intervention Compared with the model group, the horizontal and vertical motor scores of rats in the positive drug control group and the high, medium, and low dose groups of Yixin Jieyu Fang were significantly increased (P < 0.01). Compared with the positive drug group, there was no significant difference in the horizontal and vertical motor scores of rats in the high dose group of Yixin Jieyu Fang (P > 0.05), while the horizontal and vertical motor scores of rats in the medium and low dose groups of Yixin Jieyu Fang were significantly decreased (P < 0.01). Compared with the high dose group of Yixin Jieyu Fang, the horizontal motor scores of rats in the medium and low dose groups of Yixin Jieyu Fang were significantly decreased (P < 0.01), but there was no significant difference in the vertical motor scores (P > 0.05). There was no significant difference in horizontal and vertical motor scores between the medium and low dose groups of Yixin Jieyu Fang (P > 0.05). See Figure 10 .

[0043] 3.3.2 Sugar Water Preference Test (1) Sugar water preference test of rats in different groups after myocardial infarction modeling and before depression modeling There were no statistically significant differences in total fluid consumption, sucrose consumption, pure water consumption, and sucrose preference index among the rat groups before and after myocardial infarction modeling and depression modeling (P > 0.05). See Figure 11 .

[0044] (2) Sugar water preference test of rats in each group after 28 days of depression modeling Compared with the sham-operated group, the total fluid consumption, saccharide consumption, and saccharide preference index of rats in the simple depression group and the model group were significantly decreased, while the pure water consumption was significantly increased (P < 0.01). Compared with the simple AMI group, the total fluid consumption, saccharide consumption, and saccharide preference index of rats in the simple depression group were significantly decreased, while the pure water consumption was significantly increased (P < 0.01). Compared with the model group, the total fluid consumption, saccharide consumption, and saccharide preference index of rats in the simple AMI group and the simple depression group were significantly increased, while the pure water consumption was significantly decreased (P < 0.01). Pairwise comparisons among the model group, the positive control group, and the high, medium, and low dose groups of Yixin Jieyu Fang showed no statistically significant differences in total fluid consumption, saccharide consumption, pure water consumption, and saccharide preference index (P > 0.05). See Figure 12 .

[0045] (3) Sugar water preference test of rats in each group 14 days after drug intervention Compared with the model group, the total fluid consumption of the positive drug control group and the high- and medium-dose groups of Yixin Jieyu Fang was significantly increased (P < 0.05); the saccharide consumption and saccharide preference index of the positive drug control group and the high-, medium-, and low-dose groups of Yixin Jieyu Fang were all significantly increased (P < 0.05), while the pure water consumption was significantly decreased (P < 0.05). Compared with the positive drug group, there were no significant differences in total fluid consumption, saccharide consumption, pure water consumption, and saccharide preference index in the high-dose group of Yixin Jieyu Fang (P > 0.05); while the total fluid consumption, saccharide consumption, and saccharide preference index of the medium- and low-dose groups of Yixin Jieyu Fang were significantly lower (P < 0.05), while the pure water consumption was significantly increased (P < 0.05). Compared with the high-dose group of Yixin Jieyu Fang, the total fluid consumption of the low-dose group was significantly lower (P < 0.05), but there was no statistically significant difference in total fluid consumption between the medium-dose group (P > 0.05). Both the medium- and low-dose groups of Yixin Jieyu Fang showed decreased saccharide consumption and saccharide preference index (P < 0.05), while pure water consumption increased (P < 0.05). Between the medium- and low-dose groups, the medium-dose group showed significantly higher total fluid consumption, saccharide consumption, and saccharide preference index than the low-dose group (P < 0.05), but there was no significant difference in pure water consumption between the two groups (P > 0.05). See Figure 13 .

[0046] 3.3.3 Weight and weight gain (1) Comparison of body weight of rats in different groups after myocardial infarction modeling and before depression modeling There were no significant differences in body weight among the groups of rats before and after myocardial infarction modeling of depression (P > 0.05), indicating that after behavioral screening and randomization, the groups of rats were similar in body weight and comparable. See Figure 14 .

[0047] (2) Comparison of body weight of rats in different groups after 28 days of depression modeling Compared with the sham-operated group, there was no significant difference in body weight and weight gain among rats in the simple AMI group (P > 0.05). However, rats in the simple depression group and the model group had lighter body weight and slower weight gain, with statistically significant differences (P < 0.01). Compared with the simple AMI group, rats in the simple depression group had even lighter body weight and slower weight gain, with statistically significant differences (P < 0.01). Compared with the model group, rats in the simple AMI group and the simple depression group had heavier body weight and greater weight gain, with statistically significant differences (P < 0.05). Pairwise comparisons among the model group, the positive drug control group, and the high, medium, and low dose groups of Yixin Jieyu Fang showed no statistically significant differences in rat body weight and weight gain (P > 0.05). See Figure 15 .

[0048] (3) Comparison of rat body weight in each group after 14 days of drug intervention Compared with the model group, rats in the positive drug control group and the high, medium, and low dose groups of Yixin Jieyu Fang were heavier and had a significant increase in body weight (P < 0.01). Compared with the positive drug control group, there was no significant difference in body weight and weight gain among rats in the high dose group of Yixin Jieyu Fang (P > 0.05), but the medium and low dose groups of Yixin Jieyu Fang had lower body weight and slower weight gain, with statistically significant differences (P < 0.01). Compared with the high dose group of Yixin Jieyu Fang, the medium and low dose groups had lighter body weight and slower weight gain, with statistically significant differences (P < 0.05). There was no significant difference in body weight and weight gain among the medium and low dose groups of Yixin Jieyu Fang (P > 0.05). See Figure 16 .

[0049] 3.4 Effects of Yixin Jieyu Formula on 5-HT Content in the Hippocampus of Depressed Rats After AMI Compared with the sham-operated group, the hippocampal 5-HT content in rats in the simple depression group and the model group was significantly decreased (P < 0.01); compared with the simple AMI group, the hippocampal 5-HT content in rats in the simple depression group was significantly decreased (P < 0.01); compared with the model group, the hippocampal 5-HT content in rats in the simple AMI group, the simple depression group, the positive drug control group, and the high, medium, and low dose groups of Yixin Jieyu Fang was significantly increased (P < 0.05); compared with the positive drug control group, there was no significant difference in hippocampal 5-HT content in the high dose group of Yixin Jieyu Fang (P > 0.05), but it was significantly higher than that in the medium and low dose groups of Yixin Jieyu Fang (P < 0.01); the hippocampal 5-HT content in the high dose group of Yixin Jieyu Fang was significantly higher than that in the medium and low dose groups of Yixin Jieyu Fang (P < 0.01). See Figure 17 .

[0050] 3.5 Correlation analysis of serum myocardial injury markers troponin T (cTnT), creatine kinase isoenzyme (CK-MB) and hippocampal 5-HT Serum myocardial injury markers cTnT, CK-MB, and hippocampal 5-HT were all continuous variables. Pearson or Spearman correlation analysis showed that serum cTnT in depressed rats after acute myocardial infarction (AMI) was significantly negatively correlated with hippocampal 5-HT (P < 0.01); serum CK-MB was not correlated with hippocampal 5-HT (P > 0.05). See Table 3.

[0051] Table 3. Correlation analysis of serum cTnT, CK-MB and hippocampal 5-HT

[0052] 3.6 Correlation analysis of serum inflammatory biomarkers TNF-α, IL-6, IL-1β, AKT, PTGS2 and hippocampal 5-HT Serum inflammatory biomarkers TNF-α, IL-6, IL-1β, AKT, PTGS2, and hippocampal 5-HT were all continuous variables. Correlation analysis showed that serum TNF-α, IL-6, IL-1β, and PTGS2 were significantly negatively correlated with hippocampal 5-HT in depressed rats after acute myocardial infarction (P < 0.01); serum AKT was positively correlated with hippocampal 5-HT (P < 0.05). See Table 4.

[0053] Table 4. Correlation between serum TNF-α, IL-6, IL-1β, AKT, PTGS2 and hippocampal 5-HT

[0054] 3.7 Effects of Yixin Jieyu Formula on the expression of inflammatory biomarkers TNF-α, IL-6, IL-1β, AKT, and PTGS2 mRNA in the marginal zone and hippocampus of depressed rats after acute myocardial infarction (AMI). 3.7.1 Compared with the sham surgery group, the expression of TNF-α, IL-6, IL-1β, AKT, and PTGS2 mRNA in the borderline zone of myocardial infarction was significantly increased in the isolated AMI group, isolated depression group, and model group (P < 0.01), while the expression of AKT mRNA was significantly decreased (P < 0.01). The expression of TNF-α, IL-6, IL-1β, and PTGS2 mRNA in the isolated depression group was significantly lower than that in the isolated AMI group (P < 0.01), while the expression of AKT mRNA was not significantly different from that in the isolated AMI group (P > 0.05).

[0055] Compared with the model group, the expression of TNF-α mRNA, IL-6 mRNA, IL-1β mRNA, and PTGS2 mRNA was significantly decreased in the simple AMI group, the simple depression group, the positive drug control group, and the high and medium dose groups of Yixin Jieyu Fang (P < 0.01), while the expression of AKT mRNA was significantly increased (P < 0.01). In the low dose group of Yixin Jieyu Fang, the expression of TNF-α mRNA and PTGS2 mRNA was significantly decreased (P < 0.01), the expression of IL-1β mRNA was significantly decreased (P < 0.05), and there was no significant difference in the expression of IL-6 mRNA and AKT mRNA (P > 0.05). The above results suggest that, compared with rats with simple AMI and simple depression, rats with post-AMI depression showed significantly increased expression of inflammatory biomarkers TNF-α, IL-6, IL-1β, and PTGS2 mRNA in the peri-infarction zone, and significantly decreased expression of AKT mRNA. Yixin Jieyu Decoction could significantly reverse the expression of inflammatory biomarkers above the peri-infarction zone in rats with post-AMI depression, alleviating the inflammatory response. Compared with the positive control group, there were no significant differences in the expression of TNF-α mRNA, IL-6 mRNA, IL-1β mRNA, AKT mRNA, and PTGS2 mRNA in the high-dose group of Yixin Jieyu Decoction (P > 0.05); however, the expression of TNF-α mRNA, IL-6 mRNA, IL-1β mRNA, and PTGS2 mRNA in the medium- and low-dose groups of Yixin Jieyu Decoction was significantly higher than that in the high-dose group (P < 0.01), and the expression of AKT mRNA was significantly lower (P < 0.01). See Figure 18 (a), (c), (e), (g), (i). 3.7.2 Expression of TNF-α, IL-6, IL-1β, AKT, and PTGS2 mRNA in the hippocampus Compared with the sham surgery group, the expression of TNF-α mRNA, IL-6 mRNA, IL-1β mRNA, and PTGS2 mRNA in the hippocampus of the simple AMI group, the simple depression group, and the model group was significantly increased (P < 0.01), and the expression of AKT mRNA was significantly decreased (P < 0.01). The expression of TNF-α mRNA, IL-6 mRNA, IL-1β mRNA, and AKT mRNA in the simple depression group was significantly lower than that in the simple AMI group (P < 0.01), while there was no significant difference in PTGS2 mRNA expression between the two groups (P > 0.05).

[0056] Compared with the model group, the expression of TNF-α mRNA, IL-6 mRNA, IL-1β mRNA, and PTGS2 mRNA was significantly decreased in the simple AMI group, the simple depression group, the positive drug control group, and the high, medium, and low dose groups of Yixin Jieyu Fang (P < 0.01), while the expression of AKT mRNA was significantly increased (P < 0.01). These results suggest that, compared with simple AMI and simple depression rats, rats with depression after AMI showed significantly increased expression of the inflammatory biomarkers TNF-α, IL-6, IL-1β, and PTGS2 mRNA in the hippocampus, and significantly decreased expression of AKT mRNA. Yixin Jieyu Fang can significantly reverse the expression of these inflammatory biomarkers mRNA in the hippocampus of rats with depression after AMI, and the trend is consistent with that of the myocardial infarction borderline zone, thus exerting an anti-inflammatory effect. Compared with the positive control group, the high-dose group of Yixin Jieyu Fang showed significantly increased expression of TNF-α mRNA and IL-1β mRNA (P < 0.01), significantly decreased expression of AKT mRNA (P < 0.01), and no significant difference in PTGS2 mRNA expression between the two groups (P > 0.05). However, the medium- and low-dose groups of Yixin Jieyu Fang showed significantly increased expression of TNF-α mRNA, IL-6 mRNA, and PTGS2 mRNA compared with the high-dose group (P < 0.01), and significantly decreased expression of AKT mRNA (P < 0.01). There was no significant difference in IL-1β mRNA expression between the high- and medium-dose groups of Yixin Jieyu Fang (P > 0.05). See Figure 18 (b), (d), (f), (h), (j).

[0057] 3.8 Effects of Yixin Jieyu Formula on the expression of inflammatory biomarkers TNF-α, IL-6, IL-1β, AKT, and PTGS2 proteins in the marginal zone of myocardial infarction and hippocampus of depressed rats after acute myocardial infarction (AMI). 3.8.1 Expression of TNF-α, IL-6, IL-1β, AKT, and PTGS2 proteins in the borderline region of myocardial infarction Compared with the sham surgery group, the expression of TNF-α, IL-6, IL-1β, and PTGS2 proteins was significantly increased in the simple AMI group, the simple depression group, and the model group (P < 0.01), while the expression of AKT protein was significantly decreased (P < 0.01). The expression of TNF-α, IL-6, IL-1β, and AKT proteins in the simple depression group was not significantly different from that in the simple AMI group (P > 0.05), while the expression of PTGS2 protein was significantly lower in the simple depression group than in the simple AMI group (P < 0.01).

[0058] Compared with the model group, PTGS2 protein expression was significantly decreased in the AMI group (P < 0.01), and TNF-α and PTGS2 protein expression was significantly decreased in the depression group (P < 0.05). In the positive drug control group and the high, medium, and low dose groups of Yixin Jieyu Fang, TNF-α, IL-6, IL-1β, and PTGS2 protein expression was significantly decreased (P < 0.01), while AKT protein expression was significantly increased in the positive drug control group and the high and medium dose groups of Yixin Jieyu Fang (P < 0.01). These results suggest that, compared with rats with simple AMI and simple depression, rats with depression after AMI showed significantly increased expression of inflammatory biomarkers TNF-α and PTGS2 proteins in the myocardial infarction borderline zone. Yixin Jieyu Fang can significantly reverse the expression of inflammatory biomarkers TNF-α, IL-6, IL-1β, AKT, and PTGS2 proteins in the myocardial infarction borderline zone of rats with depression after AMI, exerting an anti-inflammatory effect. Compared with the positive control group, the high-dose group of Yixin Jieyu Fang showed significantly increased expression of TNF-α, IL-6, and IL-1β proteins (P < 0.05), significantly decreased AKT protein expression (P < 0.01), and no significant difference in PTGS2 protein expression (P > 0.05). There were no significant differences in IL-6, IL-1β, AKT, and PTGS2 protein expression between the high- and medium-dose groups of Yixin Jieyu Fang (P > 0.05). The medium- and low-dose groups of Yixin Jieyu Fang showed significantly higher TNF-α protein expression than the high-dose group (P < 0.01). See [link / reference needed]. Figure 19 , Figure 21 (a), (c), (e), (g), (i).

[0059] 3.8.2 Expression of TNF-α, IL-6, IL-1β, AKT, and PTGS2 proteins in the hippocampus Compared with the sham surgery group, the expression of TNF-α, IL-6, IL-1β, and PTGS2 proteins was significantly increased in the simple AMI group, the simple depression group, and the model group (P < 0.01), while the expression of AKT protein was significantly decreased (P < 0.01). The expression of TNF-α, IL-6, IL-1β, and AKT proteins in the simple depression group was not significantly different from that in the simple AMI group (P > 0.05), while the expression of PTGS2 protein was significantly lower in the simple depression group than in the simple AMI group (P < 0.05).

[0060] Compared with the model group, the expression of TNF-α, IL-1β, and PTGS2 proteins in rats with simple AMI and simple depression was significantly decreased (P < 0.05), while there was no significant difference in the expression of IL-6 and AKT proteins (P > 0.05). In the positive drug control group and the high, medium, and low dose groups of Yixin Jieyu Fang, the expression of TNF-α, IL-6, IL-1β, and PTGS2 proteins was significantly decreased (P < 0.01), while the expression of AKT protein was significantly increased (P < 0.01). These results suggest that, compared with rats with simple AMI and simple depression, rats with depression after AMI showed significantly increased expression of the inflammatory biomarkers TNF-α, IL-1β, and PTGS2 proteins in the hippocampus. Yixin Jieyu Fang can significantly reverse the expression of these inflammatory biomarkers in the hippocampus of rats with depression after AMI, and the trend is consistent with that of the myocardial infarction borderline zone, thus alleviating the inflammatory response. Compared with the positive control group, the high-dose group of Yixin Jieyu Fang showed significantly increased expression of TNF-α, IL-6, and IL-1β proteins (P < 0.05), while there was no significant difference in AKT and PTGS2 protein expression (P > 0.05). There was no significant difference in TNF-α, IL-6, IL-1β, and AKT protein expression between the high- and medium-dose groups of Yixin Jieyu Fang (P > 0.05), but the PTGS2 protein expression in the high-dose group was significantly lower than that in the medium-dose group (P < 0.05). See Figure 20 , Figure 21 (b), (d), (f), (h), (j).

[0061] In summary, Yixin Jieyu Formula can improve cardiac function and depressive-like behavior in rats with post-AMI depression, reduce myocardial cell morphological damage, inflammatory cell infiltration, and myocardial fibrosis; Yixin Jieyu Formula can simultaneously regulate key inflammatory biomarker targets TNF-α, AKT, IL-1β, IL-6, and PTGS2 in the heart and hippocampus, exert anti-inflammatory effects, and treat post-AMI depression.

[0062] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating post-acute myocardial infarction depression, characterized in that: It consists of 30 g of raw Astragalus membranaceus, 10 g of Cyperus rotundus, 20 g of Ligusticum chuanxiong, 10 g of Coptis chinensis, and 10 g of Bupleurum chinense.

2. The traditional Chinese medicine composition for treating post-acute myocardial infarction depression according to claim 1, wherein the traditional Chinese medicine composition is in the form of granules or decoction.

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