Application of rhamnoside vitexin in improvement of doxorubicin-induced cardiotoxicity

Abstract

The invention discloses application of rhamnoside vitexin to improvement of doxorubicin-induced cardiotoxicity, and belongs to the technical field of biological medicines. The invention provides the effect of rhamnoside vitexin in improving doxorubicin-induced cardiotoxicity for the first time. Experiments show that the rhamnoside vitexin can significantly reduce the death rate of doxorubicin-induced cardiotoxicity mice, increase the heart weight / tibia length value of the doxorubicin-induced cardiotoxicity mice, significantly improve the heart function indexes of the doxorubicin-induced cardiotoxicity mice, reduce the inflammatory factor level and myocardial enzyme activity, and improve the curative effect of the doxorubicin-induced cardiotoxicity mice. Myocardial injury and mitochondrial injury of doxorubicin-induced cardiotoxic mice are relieved, and a solid pharmacodynamic basis is provided for research, development and application of related drugs.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technology, and particularly to the application of vitexin-rhamnoside in improving doxorubicin-induced cardiotoxicity. Background Art

[0002] Doxorubicin (ADM) is a widely used antitumor antibiotic, which is mainly used for the treatment of various cancers such as acute leukemia (including lymphocytic and granulocytic), malignant lymphoma, breast cancer, bronchogenic carcinoma (undifferentiated small cell and non-small cell), ovarian cancer, soft tissue sarcoma, osteosarcoma, rhabdomyosarcoma, Ewing's sarcoma, blastoma, neuroblastoma, bladder cancer, thyroid cancer, prostate cancer, head and neck squamous cell carcinoma, testicular cancer, gastric cancer, liver cancer, etc. Doxorubicin belongs to cytotoxic drugs, and its mechanism of action is to kill tumor cells by inhibiting the synthesis of RNA and DNA.

[0003] However, in clinical applications, while doxorubicin exerts its antitumor effect, there are also various adverse reactions. The side effects of doxorubicin include bone marrow hematopoietic function inhibition (manifested as thrombocytopenia and leukopenia), cardiotoxicity (heart failure may occur in severe cases), nausea, vomiting, stomatitis, alopecia, high fever, phlebitis, and skin pigmentation, etc., among which cardiotoxicity is more dangerous. The cardiotoxicity of doxorubicin can be manifested as acute or chronic, including left ventricular dysfunction, dilated cardiomyopathy, and heart failure. Therefore, finding drugs that can reduce the cardiotoxicity of doxorubicin is very important for its clinical application.

[0004] Vitexin-rhamnoside (VR) is an active ingredient extracted from hawthorn leaves and belongs to flavonoid compounds. Due to its pharmacological effects, vitexin-rhamnoside has broad application prospects in the field of medical research, especially in the treatment of cardiovascular diseases and cancers. In experimental studies, vitexin-rhamnoside has shown positive effects on cardiac hemodynamics, can significantly increase cardiac output and stroke volume, and reduce total peripheral resistance, and can strongly inhibit the synthesis of human breast cancer cell DNA, showing anti-cancer potential. At present, there is no research report on the prevention and treatment of doxorubicin-induced cardiotoxicity by vitexin-rhamnoside. Summary of the Invention

[0005] The purpose of the present invention is to provide the application of vitexin-rhamnoside in improving doxorubicin-induced cardiotoxicity to solve the problems existing in the above-mentioned prior art. The present invention first proposes the role of vitexin-rhamnoside in improving doxorubicin-induced cardiotoxicity, providing a solid pharmacodynamic basis for the research and development and application of related drugs.

[0006] To achieve the above purpose, the present invention provides the following solutions:

[0007] The present invention provides the use of vitexin-rhamnoside in the preparation of a drug for improving doxorubicin-induced cardiotoxicity.

[0008] Optionally, vitexin-rhamnoside exerts its function of improving cardiotoxicity by reducing the levels of inflammatory factors and myocardial enzyme activities, increasing cardiac function indexes, and repairing myocardial damage.

[0009] Furthermore, the repair of myocardial damage is the repair of mitochondrial damage in myocardial tissue.

[0010] Optionally, the drug further comprises a pharmaceutically acceptable excipient.

[0011] Optionally, the excipient includes a diluent, a binder, a wetting agent, a lubricant, a disintegrant, an emulsifier, a solubilizer, a preservative, a pH regulator, an osmotic pressure regulator, a surfactant, a coating material, an antioxidant or a buffer.

[0012] Optionally, the dosage form of the drug includes a suspension, a granule, a capsule, a powder, a tablet, a dripping pill, a drop, a suppository or an aerosol.

[0013] Optionally, the administration route of the drug includes oral administration, sublingual administration, nasal administration or nebulized administration.

[0014] The present invention also provides the use of vitexin-rhamnoside in the preparation of a drug for treating myocardial damage.

[0015] Optionally, the myocardial damage is caused by doxorubicin.

[0016] Optionally, vitexin-rhamnoside exerts its function of treating myocardial damage by repairing mitochondrial damage in myocardial tissue.

[0017] The present invention discloses the following technical effects:

[0018] The present invention first proposes the role of vitexin-rhamnoside in improving doxorubicin-induced cardiotoxicity. Experiments show that vitexin-rhamnoside can significantly reduce the mortality rate of mice with doxorubicin-induced cardiotoxicity, increase the value of heart weight / tibia length of mice with doxorubicin-induced cardiotoxicity, significantly improve the cardiac function indexes of mice with doxorubicin-induced cardiotoxicity, reduce the levels of inflammatory factors and myocardial enzyme activities, alleviate myocardial damage and mitochondrial damage in mice with doxorubicin-induced cardiotoxicity, and provide a solid pharmacodynamic basis for the research and development and application of related drugs. Description of the Drawings

[0019] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the accompanying drawings required for the embodiments. Obviously, the accompanying drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other accompanying drawings can be obtained based on these drawings.

[0020] Figure 1 Graphs of the basic physical and blood indexes of each group of mice; among them, A is the flow chart of the animal experiment of the present invention; B is the survival curve graph of the mice in each experimental group; C is the anatomical graph of the hearts of the mice in each experimental group; D is the ratio of the heart weight to the tibia length of the mice in each experimental group; E - H are successively the detection result graphs of serum TNF-α, IL-6, IL-1β, and LDH of the mice in each experimental group;

[0021] Figure 2 Echocardiogram of the mice in each experimental group;

[0022] Figure 3 Schematic diagrams of the ejection fraction (A), left ventricular fractional shortening (B), end - systolic left ventricular internal diameter (C), end - systolic left ventricular volume (D), heart rate (E), stroke volume (F), cardiac output (G), and cardiac index (H) of the mice in each experimental group;

[0023] Figure 4 HE staining graph of the mice in each experimental group;

[0024] Figure 5 Sirius red staining (A) and fibrosis quantification (B) graphs of the mice in each experimental group;

[0025] Figure 6 WGA staining (A) and myocardial size quantification (B) graphs of the mice in each experimental group;

[0026] Figure 7 TEM images of myocardial tissue mitochondria (A) and mitochondrial size quantification (B) of the mice in each experimental group. Detailed implementation manners

[0027] Now, various exemplary implementation manners of the present invention will be described in detail. This detailed description should not be considered as a limitation of the present invention, but should be understood as a more detailed description of certain aspects, characteristics, and implementation schemes of the present invention.

[0028] It should be understood that the terms used in this invention are only for describing specific embodiments and are not intended to limit the invention. Additionally, for the numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any intermediate value within any stated value or stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0029] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which this invention pertains. Although this invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein can also be used in the implementation or testing of this invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the documents. In case of conflict with any incorporated document, the content of this specification shall prevail.

[0030] Without departing from the scope or spirit of this invention, various improvements and changes can be made to the specific embodiments of the specification of this invention, which are obvious to those skilled in the art. Other embodiments obtained from the specification of this invention are obvious to those skilled in the art. The specification and examples of this invention are merely exemplary.

[0031] Regarding the use of "comprising", "including", "having", "containing", etc. herein, they are all open-ended terms, meaning including but not limited to.

[0032] The vitexin rhamnoside described in this invention has a molecular weight of 578.52 and a chemical formula of C 27 H 30 O 14 , with a CAS number of 64820-99-1, and the structural formula is as follows:

[0033]

[0034] The vitexin rhamnoside used in the examples of this invention was purchased from Yuanye Bio-Technology Co., Ltd., and the product catalog number is: B20878.

[0035] The doxorubicin used in the examples of this invention was purchased from Solarbio, and the product catalog number is: D8740.

[0036] Unless otherwise specified, the experimental methods used in the examples of this invention are all conventional methods, and the materials, reagents, etc. used can all be obtained through commercial channels.

[0037] Example 1

[0038] I. Experimental method

[0039] 1. Drug preparation

[0040] Dissolve doxorubicin in 0.9% physiological saline, dissolve vitexin-rhamnoside in DMSO solution, and dilute it with 0.9% physiological saline.

[0041] 2. Animals

[0042] 8-week-old SPF-grade male C57Bl / 6J mice were purchased from Beijing Speywood Biotechnology Co., Ltd. and housed in the SPF-grade experimental animal facility of China Agricultural University. The light and dark periods were 12 h each day, the breeding room temperature was 23℃ - 25℃, and the relative air humidity was 40% - 60%. According to the principle of simulating day and night lighting, deionized water was freely available for drinking and ordinary mouse feed was available for ingestion.

[0043] 3. Preparation of heart failure animal model

[0044] All animal experiments were conducted in accordance with the guidelines for the use and care of laboratory animals and were approved by the Ethics Committee of China Agricultural University. During the preparation of the animal model, doxorubicin at a dose of 3 mg / kg was intraperitoneally injected every two days for two consecutive weeks, with a cumulative dose of 21 mg / kg to prepare a chronic heart failure mouse model.

[0045] 4. Animal grouping and administration

[0046] After 5 days of adaptive feeding and observation, all mice were numbered from smallest to largest according to body weight. According to the random number table method, the mice were divided into 3 groups, with 12 mice in each group. The specific grouping and administration were as follows:

[0047] Model group (DOX group): Doxorubicin at a dose of 3 mg / kg was intraperitoneally injected every two days for two consecutive weeks, with a cumulative dose of 21 mg / kg.

[0048] Blank control group (Control group): Physiological saline.

[0049] Vitexin-rhamnoside intervention group (DOX + VR group): Doxorubicin at a dose of 3 mg / kg was intraperitoneally injected every two days for 2 weeks, with a cumulative dose of 21 mg / kg. At the same time, vitexin-rhamnoside at a dose of 25 mg / kg was intraperitoneally injected once every two days for 5 weeks.

[0050] The schematic diagram of the animal experiment process is as shown in Figure 1 A of. The blank control group, model group, and vitexin-rhamnoside intervention group were sacrificed 40 days after administration.

[0051] 5. Observation indicators

[0052] (1) Body weight changes, mortality, heart weight, and tibia length of mice.

[0053] (2) Measuring TNF-α, IL-6, IL-1β, and LDH in mouse serum by enzyme-linked immunosorbent assay (ELISA):

[0054] Reagent preparation: Take out the tumor necrosis factor α-induced protein 3 (Tnfaip3) test kit (H691-1-2), interleukin-6 (IL-6) test kit (H007-1-2), interleukin-1β (IL-1β) test kit (H002-1-2), and lactate dehydrogenase (LDH) kit (A020-2-2) from the 4°C refrigerator and place them at room temperature (20-25°C) for 30 minutes before measurement. All the test kits were purchased from Nanjing Jiancheng Bioengineering Institute.

[0055] Sample preparation: Take out the aliquoted serum from the -80°C refrigerator and place it at room temperature. Wait until it is completely dissolved before use.

[0056] Working solution preparation: Dilute the 20× washing buffer in the test kit and distilled water in a ratio of 1:20 for use.

[0057] Detection setting grouping: Set the standard product group, sample group, and blank group.

[0058] Sample addition: Take out the enzyme-linked immunosorbent assay (ELISA) plate and add 100 μL of the standard product solution to the blank micro-wells in the order of the standard products; add 100 μL of the sample to the blank micro-wells, add 100 μL of distilled water to the blank control, and add 50 μL of the enzyme-labeled solution to the remaining wells except the blank control well.

[0059] Incubation: Seal the ELISA plate with sealing film and incubate it in a 37°C constant temperature incubator for 1 hour.

[0060] Washing solution preparation: Dilute the concentrated washing solution with distilled water in a volume ratio of 1:100 to prepare 500 mL of washing solution for use.

[0061] Plate washing: Remove the sealing film, discard the old liquid, pat dry with absorbent paper, add 300 μL of washing solution to each well, let it stand for 30 seconds, then discard the washing solution, and pat dry thoroughly with absorbent paper. Repeat this step 3 times.

[0062] Color development: First add 50 μL of color developer A to each well, then add 50 μL of color developer B, and then place it in a 37°C constant temperature incubator for 10 minutes for color development in the dark.

[0063] Terminate the reaction: Add 50 μL of termination solution to each well to terminate the reaction, and use an enzyme-linked immunosorbent assay (ELISA) reader to detect the OD value of each well at a wavelength of 450 nm.

[0064] (3) Evaluating the cardiac structure and function of mice by echocardiography:

[0065] On the 40th day of drug administration, the Vevo 1100 high-resolution small animal color Doppler imaging system was used to detect the cardiac function of mice in each group. The main measurements included the left ventricular anterior wall thickness at end-systole (LVAWs), the left ventricular posterior wall thickness at end-systole (LVPWs), the left ventricular internal diameter at end-systole (LVIDs), the left ventricular internal diameter at end-diastole (LVIDd), the left ventricular anterior wall thickness at end-diastole (LVAwd), the left ventricular posterior wall thickness at end-diastole (LVPWd). The left ventricular end-systolic volume (LVESV) and the left ventricular end-diastolic volume (LVEDV) were calculated. And the left ventricular ejection fraction (EF), fractional shortening (FS), stroke volume (SV), cardiac output (CO), and cardiac index (CI) of mice were calculated based on the above measurement results. When measuring each mouse, the results of 3 consecutive cardiac cycles were measured and the average value was taken as the statistical value.

[0066] (4) Evaluation of pathological indicators

[0067] Preparation of heart sections:

[0068] 1) Dehydration and infiltration with wax: The heart was taken out of the tissue fixative, placed in an embedding cassette and marked. Dehydration and infiltration with wax were carried out, and the steps are shown in Table 1:

[0069] Table 1 Steps of dehydration and infiltration with wax

[0070]

[0071]

[0072] 2) Tissue embedding: First, the melted paraffin was poured into the mold. The tissue was carefully taken out with heated forceps and quickly placed into the mold with the cross-section facing up. Wait until the paraffin solidifies slightly, then cover the base of the embedding cassette, and continue to add wax until the base of the embedding cassette is submerged. Place it at room temperature to cool and solidify.

[0073] 3) Sectioning and spreading: The embedded wax block was taken out of the mold and placed on a biological tissue freezing table. After the wax block cooled, it was fixed on a paraffin slicer. First, adjust the section thickness to trim the section. When a complete heart appeared, continuous sectioning began. Each section was 5 μm thick. The section was taken off with forceps and flattened on the water surface of the spreading machine. The wrinkles were unfolded with a curved forceps. The spreading temperature was 42 °C.

[0074] 4) Floating and baking the sections: When the section was completely spread, it was quickly picked up with a glass slide, and the excess water was blotted with filter paper. The number was marked, and then it was placed in a 37 °C constant temperature oven and dried overnight.

[0075] 5) Dewaxing and rehydration: The steps are shown in Table 2:

[0076] Table 2 Steps of dewaxing and rehydration

[0077]

[0078] Pathological staining:

[0079] a. Hematoxylin and eosin (HE) staining

[0080] 1) Stain with hematoxylin solution for 4 min, and wash off the floating stain with distilled water.

[0081] 2) Differentiate with the differentiation solution for 3 min, and immerse in tap water 2 times, 2 min each time.

[0082] 3) Stain with eosin staining solution for 1 min, and wash off the excess floating stain with distilled water.

[0083] 4) Rapid dehydration and clearing, the steps are shown in Table 3:

[0084] Table 3 Steps of rapid dehydration and clearing

[0085]

[0086] 5) Mount the section with neutral balsam, and observe under an optical microscope after drying.

[0087] b. Modified Sirius red staining

[0088] 1) Mix equal amounts of hematoxylin stock solution (A1) and hematoxylin diluent (A2) in the modified Sirius red staining kit (G1472, Solarbio) and use it immediately after preparation.

[0089] 2) Stain with the prepared hematoxylin staining solution for 5 min, wash with distilled water for 15 s to wash off the excess staining solution.

[0090] 3) Wash with tap water to blue back for 5 min, wash with distilled water 3 times, 10 s each time.

[0091] 4) Drop-stain with Sirius red staining solution for 5 min.

[0092] 5) Quickly rinse the section with distilled water to remove the excess staining solution.

[0093] 6) Perform serial ethanol rapid dehydration starting from 75% volume fraction, clear with xylene, and mount with neutral balsam, the steps are shown in Table 4.

[0094] Table 4 Steps of rapid dehydration

[0095]

[0096] c. iFluor 594 wheat germ agglutinin (WGA) conjugate staining

[0097] 1) Preparation of stock solution: Stock solution (200x) of iFluor 594 Wheat Germ Agglutinin (WGA) conjugate.

[0098] 2) Preparation of working solution: Working solution (1x) of iFluor 594 Wheat Germ Agglutinin (WGA) conjugate.

[0099] 3) Antigen retrieval: Dissolve 1 packet of palmitate in 1 L of water to prepare 0.01 M citrate buffer solution. Put the citrate (0.01 M) into a microwave oven at 100% power for 5 min first, then put the slides in and heat at 20 - 30% power for 2 min, repeat 3 times, cool to room temperature (naturally), immerse in PBS solution and wash 3 times, 5 min each time.

[0100] 4) Blocking: Take 50 μl of goat serum and dissolve it in 1 ml of PBS to prepare 5% goat serum, drop it onto the tissue, block for 30 min, and discard the residual liquid.

[0101] 5) WGA staining: Drop the WGA staining solution, incubate in the dark at a constant temperature of 37 °C for 30 min. Wash with PBS 3 times, 5 min each time.

[0102] 6) Mounting: Drop the anti-fluorescence quenching mounting medium (containing DAPI) for mounting, observe the fluorescence with a confocal microscope, and pay attention to avoiding light during the process. The excitation wavelength of WGA is 557 nm and the emission wavelength is 570 nm.

[0103] (5) Transmission Electron Microscope (TEM)

[0104] Anesthetize the animal, quickly dissect the thoracic cavity, take out the heart and place it on the wax sheet for sampling. Drop the room temperature electron microscope fixative (2.5% glutaraldehyde) on the heart, quickly cut open the ventricle transversely with a sharp blade, and select the part near the apex on the left side of the left ventricle. Immediately use a double-sided blade to gradually cut the tissue into long and thin slices of 0.5×1×2 mm in the fixative. Note that the tissue cannot be separated from the fixative during the slicing process. Use a toothpick or ophthalmic forceps to pick up 3 - 5 pieces and transfer them to a 1.5 mL centrifuge tube containing no less than 1 mL of room temperature fixative, invert several times, fill the fixative, leave at room temperature for half an hour, then transfer to a 4 °C refrigerator and store overnight, and then observe with TEM. Note that the sampling process needs to be fast, accurate, and small; it is recommended that the total time from anesthesia to putting the tissue into the centrifuge tube does not exceed 3 minutes; the fixative is 2.5% glutaraldehyde, at room temperature.

[0105] Among them, SPSS 13.0 software was used for data processing. The statistical results were expressed as mean ± standard error (±SEM). The t-test was used to analyze the differences between the two groups of data. When comparing multiple groups of data, ANOVA was used for variance analysis, and the Bonferroni test was used for further analysis and verification. A p value < 0.05 was considered to indicate a significant difference. Among them, * indicates p < 0.05, ** indicates p < 0.01, and *** indicates p < 0.001.

[0106] II. Experimental Results

[0107] The survival curves of mice in each experimental group are shown as Figure 1 shown in B of [Figure number]. The mortality rate of mice in the DOX model group was nearly 60%, while that in the VR intervention group was only 10%.

[0108] The anatomical diagrams of the hearts of mice in each experimental group and the ratio of heart weight / tibia length are shown as Figure 1 shown in C and D of [Figure number]. Compared with the blank control group, the hearts of mice became significantly smaller, and the ratio of heart weight / tibia length decreased. After VR intervention, the size of the hearts of mice recovered, and the ratio of heart weight / tibia length increased.

[0109] The levels of serum TNF-α, IL-6, IL-1β, and LDH in mice in each experimental group are shown as Figure 1 shown in E - H of [Figure number]. Compared with the blank control group, the levels of IL-6, IL-1β, TNF-α, and LDH in the DOX model group were significantly increased; compared with the DOX model group, the levels of IL-6, IL-1β, TNF-α, and LDH decreased after VR intervention. The results suggest that when the cumulative dose of DOX is 21 mg / kg, it can seriously affect cardiac function, while VR can significantly improve this situation.

[0110] The echocardiogram of mice in each experimental group is shown as Figure 2 shown in [Figure number]. The ejection fraction, left ventricular shortening fraction, end-systolic left ventricular diameter, end-systolic left ventricular volume, heart rate, stroke volume, cardiac output, and cardiac index are shown as Figure 3 shown in [Figure number]. The ventricular wall contraction and relaxation functions of mice in the blank control group were good, showing regular M-mode wave motion; compared with the blank control group, the EF and FS values of mice in the DOX model group decreased significantly, LVID;s and LVESV increased, and HR, SV, CO, and CI decreased. However, the VR group could significantly increase the EF and FS values of heart failure mice and effectively improve the ventricular wall contraction and relaxation functions. The results suggest that when the cumulative dose of DOX is 21 mg / kg, it can significantly affect the cardiac structure and function, while VR can significantly improve this situation.

[0111] The HE staining diagrams of mice in each experimental group are shown as Figure 4As shown, compared with the blank control group, the hearts of mice in the DOX model group were significantly smaller, the cardiomyocytes were atrophied, and the cell gaps were dilated. Compared with the model group, the hearts of mice in the VR intervention group became larger, and the atrophy of cardiomyocytes was significantly alleviated.

[0112] The Sirius red staining and fibrosis quantification diagrams of the myocardial tissues of mice in each experimental group are as Figure 5 shown. Compared with the blank control group, the degree of interstitial fibrosis in the myocardial tissues of the DOX model group increased, while the degree of fibrosis in the myocardial tissues of the VR intervention group was significantly weakened.

[0113] The WGA staining and myocardial size quantification diagrams of the myocardial tissues of mice in each experimental group are as Figure 6 shown. Compared with the blank control group, the cardiomyocytes in the DOX model group were significantly smaller; compared with the model group, the cardiomyocytes of mice in the VR intervention group became larger.

[0114] The TEM diagrams of mitochondria and the quantification diagrams of mitochondrial size in the myocardial tissues of mice in each experimental group are as Figure 7 shown. Compared with the blank control group, the mitochondria in the DOX model group were swollen and enlarged, accompanied by vacuolization, and the arrangement of the cristae was disordered and loose; compared with the model group, the volume of mitochondria in the VR intervention group became smaller, and the mitochondrial morphology was somewhat restored.

[0115] The above results all suggest that a cumulative DOX dose of 21 mg / kg can induce cardiac toxicity in the body, while VR can significantly improve this situation.

[0116] The embodiments described above are only descriptions of the preferred modes of the present invention, and do not limit the scope of the present invention. Without departing from the design spirit of the present invention, various deformations and improvements made by those of ordinary skill in the art to the technical solutions of the present invention shall fall within the protection scope determined by the claims of the present invention.

Claims

1. Application of rhamnoside of vitexin in the preparation of drugs for improving doxorubicin-induced cardiotoxicity.

2. The use according to claim 1, characterized in that: Vitexin rhamnoside improves cardiac toxicity by reducing the levels of inflammatory factors and myocardial enzyme activity, improving cardiac function indicators and repairing myocardial damage.

3. The use according to claim 2, characterized in that: The repairing of myocardial damage is repairing mitochondrial damage in myocardial tissue.

4. The use according to claim 1, characterized in that: The drug also includes pharmaceutically acceptable excipients.

5. The use according to claim 4, characterized in that: The auxiliary materials include diluents, adhesives, wetting agents, lubricants, disintegrants, emulsifiers, solubilizers, preservatives, pH regulators, osmotic pressure regulators, surfactants, coating materials, antioxidants or buffers.

6. The use according to claim 1, characterized in that: The dosage form of the drug includes suspension, granules, capsules, powders, tablets, pills, drops, suppositories or aerosols.

7. The use according to claim 1, characterized in that: The administration routes of the drug include oral administration, sublingual administration, nasal administration or aerosol administration.

8. Application of vitexin rhamnoside in the preparation of drugs for treating myocardial injury.

9. The use according to claim 8, characterized in that: The myocardial damage was caused by doxorubicin.

10. The use according to claim 8, characterized in that: Vitexin rhamnoside can treat myocardial damage by repairing mitochondrial damage in myocardial tissue.

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