Application of auricularia auricula polysaccharide in preparation of medicine for preventing and treating ventricular remodeling

Abstract

The invention discloses application of auricularia auricula polysaccharide in preparation of a medicine for preventing and treating ventricular remodeling. The invention relates to the field of biological medicine, and provides application of auricularia auricula polysaccharide in preparation of a product for preventing and / or treating ventricular remodeling. Auricularia auricula polysaccharide can improve ISO-induced myocardial fibrosis, myocardial injury and cardiac dysfunction of mice; and the black fungus polysaccharide can be used for alleviating oxidative stress injury by activating a Keap1 / Nrf2 / HO-1 signal channel. The medicinal value of the auricularia auricula polysaccharide is enriched, and the auricularia auricula polysaccharide can serve as a candidate medicine for clinically preventing and treating ventricular

Description

Technical Field

[0001] The invention relates to the field of biomedicine, and in particular to application of black fungus polysaccharide in preparing a drug for preventing and treating ventricular remodeling. Background Art

[0002] Heart failure (HF), abbreviated as HF, is the terminal event of various cardiovascular diseases such as myocardial infarction. It is one of the main causes of death in patients worldwide, with extremely high morbidity and mortality and extremely poor prognosis.

[0003] Drug therapy remains an important treatment for patients with chronic heart failure. The 2021 European Heart Failure Guidelines recommend the use of a quadruple standard treatment regimen: angiotensin-converting enzyme inhibitors (ACEI), beta-blockers (BBs), aldosterone receptor antagonists, angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors for the treatment of heart failure. However, although the use of these drugs has partially improved the clinical symptoms of patients with heart failure, they cannot delay the progression of the disease, and the 5-year survival rate of heart failure is still less than 50%. Moreover, the use of ACEI can induce dry cough, the use of ARNI can increase the risk of symptomatic hypotension and angioedema, and the use of BBs can aggravate bronchospasm in asthma patients. Therefore, the prevention and treatment of heart failure is an important issue that has not yet been resolved and needs to be solved urgently.

[0004] Ventricular remodeling, including myocardial hypertrophy and myocardial fibrosis, is the main pathological basis for the development of chronic heart failure and a determining factor affecting the morbidity and mortality of heart failure. The more severe the ventricular remodeling, the worse the prognosis of cardiovascular disease, which eventually leads to heart failure and death in patients. Blocking ventricular remodeling is an important part of preventing heart failure that cannot be ignored.

[0005] The occurrence and development of ventricular remodeling is an extremely complex process. At present, the mechanism of ventricular remodeling has not been fully elucidated, involving multiple disease-related signaling pathways, including overactivation of the neuroendocrine system, cardiac cell damage and apoptosis, inflammatory response, oxidative stress injury, and overactivation of cardiac fibroblasts, which lead to the loss of cardiomyocytes, hypertrophy and myocardial fibrosis, thereby inducing adverse cardiac remodeling.

[0006] Traditional Chinese medicine has attracted extensive attention and research as an alternative therapy due to its low toxicity and multiple targets. Medicinal fungi, the treasure of traditional Chinese medicine, have a long history as a medicinal material in my country. They are not only an extremely important part of my country's natural drug resources and Chinese herbal medicine, but also an important field for exploring and discovering anti-cancer drugs today. The efficacy of medicinal fungi such as Poria cocos, Ganoderma lucidum, Cordyceps sinensis, and Auricularia auricula has been recorded in the "Shennong's Herbal Classic". A large number of studies have confirmed that medicinal fungi and their active ingredients, polysaccharides, have antioxidant, immunomodulatory, hypoglycemic and hypolipidemic effects.

[0007] As a natural active substance, fungal polysaccharides have a wide range of sources and few toxic side effects, and have received extensive attention in the fields of medicine, biology and food science. Auricularia auricula ), belongs to the phylum Basidiomycetes ( Basidiomycota )、Agaricaceae( Agaricomycetes )、Auriculariales( Auriculariales )、Auriculariaceae( Auriculariaceae )、Auricularia( Auricularia Auricularia auriculariae (Auricularia auriculariae), also known as wood fungus, light wood ear, and tree ear, is a large traditional Chinese medicinal fungus. Its medicinal value was first recorded in the Chinese medicine book Shennong's Herbal Classic. Its main effects include relieving and treating vascular sclerosis and hypertension. Auricularia auriculariae polysaccharides (AAP) is the most important active ingredient in black fungus. A large number of studies have confirmed that AAP has pharmacological effects such as antioxidant, anticoagulant, anti-tumor, hypoglycemic, immune regulation, and lipid-lowering. At present, there are no reports on the possible protective effects of AAP on ventricular remodeling and its related mechanisms. Summary of the invention

[0008] The purpose of the present invention is to provide the use of black fungus polysaccharide in preparing a drug for preventing and treating ventricular remodeling.

[0009] In a first aspect, the present invention claims the use of black fungus polysaccharide in the preparation of a product for preventing and / or treating ventricular remodeling. Furthermore, the application is the use of black fungus polysaccharide as a Keap1 / Nrf2 / HO-1 signaling pathway activator in the preparation of a product for preventing and / or treating ventricular remodeling.

[0010] In the second aspect, the present invention claims the use of black fungus polysaccharide in any of the following: (A1) Preparation of products for improving cardiac dysfunction; (A2) preparing a product for improving myocardial hypertrophy; (A3) Preparing products for ameliorating myocardial damage; (A4) Preparing a product for improving myocardial fibrosis.

[0011] Furthermore, (A1) the application is the use of black fungus polysaccharide as a Keap1 / Nrf2 / HO-1 signaling pathway activator in the preparation of a product for improving cardiac dysfunction; (A2) the application is the use of black fungus polysaccharide as a Keap1 / Nrf2 / HO-1 signaling pathway activator in the preparation of a product for improving myocardial hypertrophy; (A3) the application is the use of black fungus polysaccharide as a Keap1 / Nrf2 / HO-1 signaling pathway activator in the preparation of a product for improving myocardial injury; (A4) the application is the use of black fungus polysaccharide as a Keap1 / Nrf2 / HO-1 signaling pathway activator in the preparation of a product for improving myocardial fibrosis.

[0012] In a third aspect, the present invention claims protection for the use of black fungus polysaccharide in the preparation of a product for improving oxidative stress damage.

[0013] Furthermore, the application is the use of black fungus polysaccharide as a Keap1 / Nrf2 / HO-1 signaling pathway activator in the preparation of a product for improving oxidative stress damage.

[0014] In the first to third aspects above, the product may be a medicine. Furthermore, the main active ingredient or the only active ingredient of the medicine is black fungus polysaccharide.

[0015] In a specific implementation case of the present invention, the cardiac dysfunction is isoproterenol (ISO)-induced cardiac dysfunction; the myocardial hypertrophy is ISO-induced myocardial hypertrophy; the myocardial injury is ISO-induced myocardial injury; the myocardial fibrosis is ISO-induced myocardial fibrosis; and the oxidative stress injury is ISO-induced oxidative stress injury.

[0016] In a fourth aspect, the present invention claims the use of black fungus polysaccharide as or in the preparation of an activator of the Kelch-like ECH-associated protein 1 (KEAP1) / nuclear factor E2-related factor 2 (Nrf2) / heme oxygenase 1 (HO-1) signaling pathway.

[0017] Furthermore, the main active ingredient or the only active ingredient of the activator is black fungus polysaccharide.

[0018] In a specific implementation case of the present invention, the activator of the Keap1 / Nrf2 / HO-1 signaling pathway is an activator of the Keap1 / Nrf2 / HO-1 signaling pathway under ISO induction.

[0019] As a signal pathway activator, it can be used for simple research related to the signal pathway and has nothing to do with the diagnosis and treatment of the disease.

[0020] In a fifth aspect, the present invention claims the use of black fungus polysaccharide in any of the following: (C1) preparing a product for improving ISO-induced reduction in cardiac ejection fraction (EF%) and / or fractional shortening (FS%); (C2) preparing products for improving ISO-induced increase in cardiac volume and / or cardiac mass index (heart weight / body weight); (C3) preparing a product for improving ISO-induced inflammatory infiltration and / or myocardial fiber fragmentation and / or myocardial cell necrosis; (C4) preparing a product for improving ISO-induced cardiomyocyte damage; Furthermore, the improvement of ISO-induced cardiomyocyte damage can be manifested as the improvement of ISO-induced increases in plasma lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) levels.

[0021] (C5) preparing a product for improving ISO-induced elevated expression of α-SMA and / or Collagen III in myocardial tissue; (C6) preparing a product for improving ISO-induced increase in serum malondialdehyde (MDA) content and / or decrease in glutathione (GSH) content and / or decrease in superoxide dismutase (SOD) activity; (C7) Preparing a product for improving ISO-induced increased Keap1 expression and / or decreased Nrf2 expression and / or decreased HO-1 expression in myocardial tissue.

[0022] The main active ingredient or the only active ingredient of the product is black fungus polysaccharide. The product can be a medicine or a reagent.

[0023] In a sixth aspect, the present invention claims the use of black fungus polysaccharide as a positive control drug in screening drugs for preventing and / or treating ventricular remodeling by activating the Keap1 / Nrf2 / HO-1 signaling pathway.

[0024] It should be noted that screening out drugs that exert their therapeutic effects through specific signaling pathways (understanding the drug's mechanism of action) is of great significance for guiding medication, especially combination medication.

[0025] In the above-mentioned related aspects, the black fungus polysaccharide can be a water-soluble black fungus polysaccharide extracted from the black fungus fruiting body dry powder by hot water extraction. Furthermore, the extraction and purification method of the black fungus polysaccharide can be as follows: the ratio of the black fungus fruiting body dry powder to water is 1:50 (volume ratio), the extraction is carried out in a 90°C water bath for 4 hours, the extract is precipitated with 70% (volume percentage) ethanol, and the crude black fungus polysaccharide is eluted with a DEAE-cellulose52 chromatography column.

[0026] Experiments have shown that black fungus polysaccharide can improve ISO-induced myocardial fibrosis, myocardial damage, and cardiac dysfunction in mice. And black fungus polysaccharide can reduce oxidative stress damage by activating the Keap1 / Nrf2 / HO-1 signaling pathway. The present invention enriches the medicinal value of black fungus polysaccharide and can be used as a candidate drug for preventing and treating ventricular remodeling in clinical practice. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 Black fungus polysaccharide can improve ISO-induced cardiac dysfunction in mice (detected by echocardiography). *** indicates P<0.001 compared with the control group (Con); ns indicates no significant difference compared with the model group (ISO); # indicates P<0.05 compared with the model group (ISO); ## indicates P<0.01 compared with the model group (ISO).

[0028] Figure 2 Black fungus polysaccharide can improve ISO-induced myocardial hypertrophy in mice (mouse heart photography, heart weight / body weight calculation). *** indicates P<0.001 compared with the control group (Con); ns indicates no significant difference compared with the model group (ISO); # indicates P<0.05 compared with the model group (ISO); ## indicates P<0.01 compared with the model group (ISO).

[0029] Figure 3 Black fungus polysaccharide can improve ISO-induced myocardial injury in mice (HE, Masson, and Sirius red staining of mouse myocardial tissue).

[0030] Figure 4 Black fungus polysaccharide can improve ISO-induced myocardial injury in mice (detected by mouse myocardial injury index kit). *** indicates P<0.001 compared with the control group (Con); ns indicates no significant difference compared with the model group (ISO); # indicates P<0.05 compared with the model group (ISO); ## indicates P<0.01 compared with the model group (ISO).

[0031] Figure 5 Auricularia auricularia polysaccharide can improve ISO-induced myocardial fibrosis in mice (Western Blot detection of myocardial fibrosis-related indicators in mice). *** indicates P<0.001 compared with the control group (Con); ns indicates no significant difference compared with the model group (ISO); # indicates P<0.05 compared with the model group (ISO); ## indicates P<0.01 compared with the model group (ISO).

[0032] Figure 6Black fungus polysaccharide can improve the oxidative stress damage of ISO group mice (detected by mouse oxidative stress indicator kit). *** indicates P<0.001 compared with the control group (Con); **** indicates P<0.0001 compared with the control group (Con); ns indicates no significant difference compared with the model group (ISO); # indicates P<0.05 compared with the model group (ISO); ## indicates P<0.01 compared with the model group (ISO).

[0033] Figure 7 Black fungus polysaccharide can activate the Keap1 / Nrf2 / HO-1 signaling pathway, inhibit oxidative stress and thus alleviate ISO-induced myocardial injury in mice (Western Blot detection of Keap1 / Nrf2 / HO-1 signaling pathway indicators). *** indicates P<0.001 compared with the control group (Con); ns indicates no significant difference compared with the model group (ISO); # indicates P<0.05 compared with the model group (ISO); ## indicates P<0.01 compared with the model group (ISO). DETAILED DESCRIPTION

[0034] The present invention is further described in detail below in conjunction with specific embodiments, and the examples provided are only for illustrating the present invention, rather than for limiting the scope of the present invention. The examples provided below can be used as a guide for further improvements by those of ordinary skill in the art, and do not constitute a limitation of the present invention in any way.

[0035] The experimental methods in the following examples, unless otherwise specified, are all conventional methods, and are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. The materials, reagents, etc. used in the following examples, unless otherwise specified, can all be obtained from commercial channels.

[0036] Example 1: Application of black fungus polysaccharide in preventing and treating ventricular remodeling 1. Experimental Animals Balb / c wild-type mice, male, 23-26 g, about 8-10 weeks old, were purchased from the Experimental Animal Center of Xinjiang Medical University. The mice were housed in sterile recirculating ventilation cages at a temperature of 25°C, a humidity of 50%, a 12-hour light period, and were given ample food and water.

[0037] 2. Drugs The black fungus polysaccharide (Auricularia auricular polysaccharides, AAP) of the present invention is a black fungus water-soluble polysaccharide extracted by a conventional hot water extraction method, which is specifically as follows: the ratio of black fungus fruiting body dry powder to water is 1:50 (volume ratio), extraction is carried out in a 90°C water bath for 4 hours, 70% (volume percentage) ethanol is used to precipitate the extract, crude black fungus polysaccharide is eluted by a DEAE-cellulose52 chromatography column, the content of the black fungus polysaccharide is detected by an anthrone sulfuric acid method, sterilization is carried out by filtering with a filter membrane, and the product is stored at -20°C for standby use.

[0038] 3. Animal Experiment Grouping and Dosing Method Balb / c male mice aged 8-10 weeks (average weight of about 23-26 g) were randomly divided into a control group (control), a model group (ISO), and an administration group (ISO+AAP), with 6 mice in each group.

[0039] Control group (control): normal saline was given by gavage and injected subcutaneously on the back for 7 consecutive days; Model group (ISO): normal saline was given by gavage and ISO (5 mg / kg / d) was injected subcutaneously on the back for 7 consecutive days; AAP low-dose group (ISO+50 mg / kg AAP): 50 mg / kg / d AAP was given by gavage for 9 consecutive days, and ISO (5 mg / kg / d) was injected subcutaneously on the back for 7 consecutive days starting from the 3rd day of gavage; AAP medium-dose group (ISO+100 mg / kg AAP): 100 mg / kg / d AAP was administered by gavage for 9 consecutive days, and ISO (5 mg / kg / d) was injected subcutaneously on the back for 7 consecutive days starting from the 3rd day of gavage; AAP high-dose group (ISO+50 mg / kg AAP): 150 mg / kg / d AAP was given by gavage for 9 consecutive days, and ISO (at a dose of 5 mg / kg / d) was injected subcutaneously on the back for 7 consecutive days starting from the 3rd day of gavage.

[0040] 4. Animal Materials After the mice were anesthetized, the eyeballs were removed to collect blood. The collected blood was incubated at 37°C for 1 hour, centrifuged at 3000 rpm for 15 minutes, and the upper serum was collected and stored in a -80°C refrigerator. The abdominal skin of the mice was then cut open along the midline with scissors to expose the chest cavity. The mouse auricles were removed and perfused with saline. The heart was completely dried and photographed and its weight was recorded. A quarter of the heart was cut and fixed with 4% paraformaldehyde. The rest was frozen in a -80°C refrigerator, and RNA and protein were extracted for subsequent experiments.

[0041] 5. Echocardiography Seven days after ISO modeling, the VINNO6 small animal ultrasound imager (Vinno, Suzhou, China) was used for detection using an ultra-high frequency probe with a frequency of 23 MHz. The mice were anesthetized with 1.5-2.0% isoflurane and fixed on the examination table in a supine position. The left ventricular long axis section and the left ventricular papillary muscle level were taken to measure the M-curve. The following parameters were measured using the echocardiography detection system software: left ventricular ejection fraction (EF) and left ventricular fractional shortening (FS).

[0042] 6. Determination of heart weight index (heart weight / body weight) 7 days after ISO modeling, the mice were weighed (body weight, BW). After the heart was removed, the blood in the heart cavity was washed away with pre-cooled saline, the excess glandular tissue and blood vessels around the heart were cut off, the saline on the surface of the heart was absorbed with filter paper, the heart weight (heart weight, HW) was weighed, and the ratio of heart weight to body weight (heart weight / body weight, HW / BW) was calculated.

[0043] VII. Modified Masson trichrome staining and picrosirius red staining of myocardial fibrosis Seven days after ISO modeling, the myocardium was removed and fixed in 4% paraformaldehyde solution for 24 h (volume ratio = 30:1). Myocardial tissue was removed at the maximum diameter of the myocardium and dehydrated in 70% alcohol (12 h), 80% alcohol (8 h), 95% alcohol (5 h), and 100% alcohol (4 h) and transparentized in xylene. The tissue was then immersed in wax (4 h), embedded, and paraffin sections were prepared. Continuous sections were made using an automatic paraffin sectioner (Leica 2M2255, Leica, Mannheim, Germany), with a section thickness of 5 μm.

[0044] 1. Modified Masson trichrome staining (1) Paraffin sections are routinely dewaxed to water; (2) Place the paraffin sections in Boutin solution and place in a 37°C incubator for mordanting for 2 hours, then rinse with running water until the yellow color on the sections disappears; (3) Dye with lapis lazuli blue dye for 3 minutes and then rinse with water; (4) Stain with Mayer's hematoxylin solution for 3 minutes and then rinse with water; (5) Differentiate with acidic ethanol for a few seconds and rinse with running water; (6) Dye with Ponceau fuchsin solution for 2 min and rinse with distilled water; (7) Dipping in phosphomolybdic acid solution for 2 min; (8) Pour off the supernatant and directly add aniline blue dye solution for 2 min; (9) 0.2% weak acid treatment for a few seconds; (10) 95% ethanol rapid dehydration, anhydrous ethanol dehydration; (11) Clear with xylene three times, 5 min each time, and seal with neutral gum.

[0045] 2. Sirius red staining (1) Paraffin sections are routinely dewaxed to water; (2) Stain with 0.1% picric acid picrosirius red solution for 1 h, then rinse with running water for 5 min to remove the stain from the surface of the slice; (3) Stain with Weigert's iron hematoxylin staining solution for 10-20 min; (4) Differentiation in acidic differentiation fluid for a few seconds; (5) The tap water turns blue for 10-15 minutes; (6) Dehydrate with alcohol gradient, clear with xylene three times, and seal with neutral gum.

[0046] After the above staining, the interstitial and perivascular fibrosis areas were selected for observation and photography under a 20x objective lens of a biological optical microscope. The degree of perivascular fibrosis (perivascular fibrosis, %) and interstitial fibrosis (interstitial fibrosis, %) were calculated using ImageJ 1.53c software (National Institutes of Health, Maryland, USA).

[0047] 8. HE staining of myocardial tissue Seven days after ISO modeling, the myocardium was removed and fixed in 4% paraformaldehyde solution for 24 h (volume ratio = 30:1). Then, the myocardial tissue was removed at the maximum diameter of the myocardium and dehydrated step by step with 70% alcohol (12 h), 80% alcohol (8 h), 95% alcohol (5 h), and 100% alcohol (4 h). After being transparentized with xylene, the myocardium was immersed in wax (4 h), embedded, and paraffin sections were prepared. The sections were sliced ​​continuously with a full-automatic paraffin sectioner (Leica 2M2255, Leica, Mannheim, Germany) with a thickness of 5 μm. The sections were dewaxed to water and stained with hematoxylin-eosin (HE). The whole picture of the sections at the maximum diameter of the myocardium was photographed with a stereoscope. The myocardium was observed and photographed with a biological optical microscope (BX512DP70, Olympus, Tokyo, Japan) with a 20x objective.

[0048] IX. ELISA Plasma was collected from ISO model mice, and the content of creatine kinase isoenzyme (CK-MB) in plasma was detected by enzyme-linked immunosorbent assay (Elisabet) method.

[0049] 10. Biochemical kit detection Plasma was collected from ISO model mice and the contents of lactate dehydrogenase (LDH), malondialdehyde (MDA), glutathione (GSH) and the activity of superoxide dismutase (SOD) in plasma were detected according to the instructions of the biochemical kit.

[0050] 11. Western Blot Analysis Myocardial tissues of ISO model mice were obtained, and whole proteins were extracted. The expression of CollagenⅢ, α-SMA, KEAP1, Nrf2, and HO-1 was detected by Western Blot. The samples were electrophoresed and transferred to PVDF membranes, blocked for 1 hour, rinsed with TBST, added with primary antibodies, incubated at 4 ℃ overnight, rinsed with TBST, and incubated with secondary antibodies. ECL color development, dark box exposure, optical density scanning, and semi-quantitative analysis were performed using ImageJ1.53c software (National Institutes of Health, Maryland, USA).

[0051] 12. Statistical Analysis All data are expressed as mean ± standard error. GraphPad Prism 9.0 software was used for data analysis and plotting. One-way ANOVA was used for data statistics, and Bonferroni correction was used for inter-group comparisons. P < 0.05 was considered significant.

[0052] 13. Results and Analysis 1. Black fungus polysaccharide can improve ISO-induced cardiac dysfunction in mice After 7 consecutive days of subcutaneous injection of ISO into the back of mice, cardiac function was significantly reduced, mainly reflected in the decrease of ejection fraction (EF%) and shortening fraction (FS%). In mice treated with black fungus polysaccharide pre-oral administration, EF and FS were significantly improved, indicating that black fungus polysaccharide can improve ISO-induced cardiac dysfunction in mice (see Figure 1 ).

[0053] 2. Black fungus polysaccharide can improve ISO-induced myocardial hypertrophy in mice Through the gross observation of the heart and the calculation of the heart weight index (heart weight / mouse body weight), the heart volume and heart weight index of the mice in the ISO group were significantly increased, and pre-oral administration of black fungus polysaccharide could significantly improve the cardiac hypertrophy of mice (see Figure 2 ).

[0054] 3. Black fungus polysaccharide can improve ISO-induced myocardial injury in mice The results of HE staining showed that compared with the control group, the myocardial tissue of the mice in the ISO group had obvious inflammatory infiltration, obvious myocardial fiber rupture and myocardial cell necrosis (nuclear fragmentation and nuclear dissolution), while the myocardial tissue of the mice pretreated with black fungus polysaccharide was significantly alleviated (see Figure 3 ).

[0055] The results of biochemical kits and Elisa kits showed that compared with the control group, the levels of myocardial injury indicators lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) in the plasma of ISO group mice increased significantly, while black fungus polysaccharide could significantly reduce the levels of these two indicators, indicating that black fungus polysaccharide could significantly improve ISO-induced myocardial injury in mice (see Figure 4 ).

[0056] 5. Black fungus polysaccharide can improve ISO-induced myocardial fibrosis in mice The results of Masson and Sirius red staining showed that compared with the control group, the fibrosis area in the myocardial tissue sections of the ISO group mice increased significantly (the muscle fibers were shown as red and the fiber area was shown as blue in Masson staining, and the muscle fibers were shown as yellow and the fiber area was shown as red in Sirius red staining). Auricularia auriculariae polysaccharide can alleviate ISO-induced myocardial fibrosis in mice to varying degrees (see Figure 3 ).

[0057] Western Blot results showed that the expression of extracellular matrix in the myocardial tissue of ISO group mice: α-SMA and CollagenⅢ was significantly higher than that of the control group, while low, medium and high doses of black fungus polysaccharide could reduce the expression of the above two proteins to varying degrees, proving that black fungus polysaccharide can significantly improve ISO-induced myocardial fibrosis in mice (see Figure 5 ).

[0058] 6. Black fungus polysaccharide can improve oxidative stress damage in ISO group mice The results of the biochemical kit test showed that compared with the control group, the malondialdehyde (MDA) content in the serum of the ISO group mice increased significantly, and the glutathione (GSH) content and superoxide dismutase (SOD) activity decreased significantly. Compared with the ISO group, the MDA content in the mice of each black fungus polysaccharide administration group decreased significantly, and the GSH content and SOD activity increased significantly. This indicates that black fungus polysaccharide can alleviate ISO-induced myocardial damage in mice by inhibiting oxidative stress (see Figure 6 ).

[0059] 7. Black fungus polysaccharides can activate the Keap1 / Nrf2 / HO-1 signaling pathway, inhibit oxidative stress and thus alleviate ISO-induced myocardial damage in mice Western Blot results showed that compared with the control group, the expression of Keap1 in myocardial tissue of mice in the ISO group was significantly increased, and the expression of Nrf2 and HO-1 was significantly decreased, while the content of Keap1 in the black fungus polysaccharide group was significantly decreased, and the content of Nrf2 and HO-1 was significantly increased. This shows that black fungus polysaccharide can activate the Keap1 / Nrf2 / HO-1 signaling pathway, inhibit oxidative stress, and thus reduce ISO-induced myocardial damage in mice (see Figure 7 ).

[0060] The present invention has been described in detail above. For those skilled in the art, without departing from the purpose and scope of the present invention, and without the need to carry out unnecessary experimental conditions, the present invention can be implemented in a wide range under equivalent parameters, concentrations and conditions. Although the present invention provides specific embodiments, it should be understood that the present invention can be further improved. In a word, according to the principles of the present invention, the application is intended to include any changes, uses or improvements to the present invention, including departure from the disclosed scope in the application, and changes made with conventional techniques known in the art.

Claims

1. Application of black fungus polysaccharide in the preparation of products for preventing and / or treating ventricular remodeling.

2. Application of black fungus polysaccharide in any of the following: (A1) Preparation of products for improving cardiac dysfunction; (A2) preparing a product for improving myocardial hypertrophy; (A3) Preparing products for ameliorating myocardial damage; (A4) Preparing a product for improving myocardial fibrosis.

3. Application of black fungus polysaccharide in the preparation of products for improving oxidative stress damage.

4. The use according to any one of claims 1 to 3, characterized in that: The product described is a pharmaceutical product.

5. The use according to claim 4, characterized in that: The main active ingredient or the only active ingredient of the medicine is black fungus polysaccharide.

6. Application of black fungus polysaccharide as or in the preparation of an activator of the Keap1 / Nrf2 / HO-1 signaling pathway.

7. The use according to claim 6, characterized in that: The main effective component or the only effective component of the activator is black fungus polysaccharide.

8. Application of black fungus polysaccharide in any of the following: (C1) preparing a product for improving ISO-induced reduction in cardiac ejection fraction and / or fractional shortening; (C2) preparing products for improving ISO-induced increase in cardiac volume and / or cardiac mass index; (C3) preparing a product for improving ISO-induced inflammatory infiltration and / or myocardial fiber fragmentation and / or myocardial cell necrosis; (C4) preparing a product for improving ISO-induced cardiomyocyte damage; (C5) preparing a product for improving ISO-induced elevated expression of α-SMA and / or Collagen III in myocardial tissue; (C6) preparing a product for improving ISO-induced elevated malondialdehyde content and / or decreased glutathione content and / or decreased superoxide dismutase activity in serum; (C7) Preparing a product for improving ISO-induced increased Keap1 expression and / or decreased Nrf2 expression and / or decreased HO-1 expression in myocardial tissue.

9. Application of black fungus polysaccharide as a positive control drug in screening drugs for preventing and / or treating ventricular remodeling by activating the Keap1 / Nrf2 / HO-1 signaling pathway.

10. The use according to any one of claims 1 to 9, characterized in that: The black fungus polysaccharide is a water-soluble black fungus polysaccharide extracted from black fungus fruiting body dry powder by hot water extraction.

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