Application of heart macrophage USP9X in preparation of drugs for treating ischemic heart disease as intervention target point, polypeptide P7 and application thereof

Abstract

The present application relates to the technical field of disease treatment, in particular to the application of heart macrophage USP9X as an intervention target in the preparation of a drug for treating ischemic heart disease, and a polypeptide P7 and its application. The present application finds that Ubiquitin specific peptidase 9 X-Linked (USP9X) of heart macrophage deubiquitinase is reduced in expression in the first three days after myocardial infarction (inflammatory period), inhibition of USP9X promotes the conversion of macrophages to pro-inflammatory type, and ultimately leads to adverse remodeling of the ventricle, so it can be used as an intervention target for ischemic heart disease, and then a polypeptide is screened to effectively inhibit the degradation of USP9X after myocardial infarction, thereby reducing the excessive inflammatory response of macrophages after myocardial infarction.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of disease treatment, in particular to the application of heart macrophage USP9X as an intervention target in the preparation of drugs for treating ischemic heart disease, polypeptide P7 and the application thereof. BACKGROUND

[0002] Ischemic heart disease, especially acute myocardial infarction (AMI), is one of the main causes of death in the global population. Although the acute mortality rate of acute myocardial infarction has decreased with the development of treatment strategies such as cardiac revascularization, the number of people with heart failure is steadily increasing. Ventricular pathological remodeling is the main pathological basis of heart failure after myocardial infarction and an important factor for judging prognosis. Currently, there are still few methods for improving ventricular pathological remodeling in clinical practice.

[0003] Excessive inflammatory response of some macrophages in the acute phase after myocardial infarction can lead to increased infarct size, worsening cardiac function, and heart failure. Therefore, inhibiting macrophage inflammatory response and promoting inflammation resolution are potential measures to prevent pathological remodeling after myocardial infarction. Existing treatment methods have limitations in relieving inflammation and pathological remodeling, and new effective treatment strategies need to be developed.

[0004] Polypeptides are bioactive molecules composed of two or more amino acids connected by peptide bonds, which are ubiquitous in nature and living organisms and play a key role in life activities. Polypeptide drugs are highly valued in the field of drug development due to their low dosage, strong specificity, significant efficacy, small side effects, ease of synthesis and customization, and are actively explored at various stages such as laboratory research, animal experiments and clinical trials.

[0005] Therefore, it is of great research value and application prospect to develop a polypeptide drug that blocks the recognition of USP9X by HSC70, which can effectively inhibit the degradation of USP9X after myocardial infarction and reduce the excessive inflammatory response of macrophages after myocardial infarction. SUMMARY

[0006] In order to solve the above problems, the application provides application of heart macrophage USP9X in preparation of a drug for treating ischemic heart disease as an intervention target, polypeptide P7 and application thereof, and finds that heart macrophage ubiquitin specific peptidase 9X-linked (USP9X) is reduced in expression in the first three days after myocardial infarction (inflammatory period), inhibition of USP9X promotes transformation of macrophages into proinflammatory type, and finally leads to adverse remodeling of ventricles, so that the USP9X can be used as an intervention target of ischemic heart disease, and then polypeptides are screened to effectively inhibit degradation of USP9X after myocardial infarction, so as to reduce excessive inflammatory reaction of macrophages after myocardial infarction.

[0007] In order to achieve the above object, the application provides the following technical scheme.

[0008] The application provides application of heart macrophage USP9X in preparation of a drug for treating ischemic heart disease as an intervention target.

[0009] The application further provides a polypeptide P7, and an amino acid sequence of the polypeptide P7 is YGRKKRRQRRR-DLKRQ.

[0010] The application further provides application of the polypeptide P7 in preparation of a drug for inhibiting degradation of heart macrophage USP9X.

[0011] Preferably, the polypeptide P7 inhibits degradation of heart macrophage USP9X after myocardial infarction.

[0012] The application further provides application of the polypeptide P7 in preparation of a drug for reducing combination of heart macrophage USP9X and HSC70.

[0013] The application further provides application of the polypeptide P7 in preparation of a drug for treating ischemic heart disease.

[0014] The application further provides a drug for treating ischemic heart disease, which comprises the polypeptide P7.

[0015] Preferably, the drug further comprises a pharmaceutically acceptable carrier and / or excipient.

[0016] Preferably, the drug is a drug preparation for injection, oral administration, nasal mucosa, lung, rectum, oral mucosa or skin.

[0017] Preferably, the injection comprises intramyocardial injection, intradermal injection, subcutaneous injection, intramuscular injection or intravenous injection.

[0018] Target proteins that can be specifically degraded by chaperone-mediated autophagy (CMA): target proteins carrying KFERQ sequences are recognized by chaperone HSC70 and transported to lysosomes for degradation by lysosome-associated membrane protein 2A receptors. The present application finds that the increased acetylation level of macrophage USP9X after myocardial infarction causes the exposure of KFERQ sequences, making them easily recognized by chaperone HSC70 for chaperone-mediated autophagy.

[0019] The present application finds the degradation mechanism of macrophage USP9X: the increased acetylation level of macrophage USP9X after myocardial infarction causes the exposure of KFERQ sequences, making them easily recognized by chaperone HSC70 for autophagy degradation.

[0020] The polypeptide P7 provided by the present application has good cell penetration and can efficiently enter target cells without obvious toxic side effects in an effective dose range; can effectively inhibit the degradation of USP9X in macrophages in the acute phase after myocardial infarction, thereby inhibiting the inflammatory response; can effectively inhibit the pathological remodeling after myocardial infarction and improve cardiac function.

[0021] The expression of cardiac macrophage USP9X decreases in the inflammatory period after myocardial infarction, and the inhibition of USP9X promotes the inflammatory response of macrophages and aggravates pathological cardiac remodeling.

[0022] The present application explains the degradation mechanism of macrophage USP9X: the 2414 site of USP9X is acetylated and modified to form KFERQ sequences in the acute inflammatory period after myocardial infarction, making it easily recognized by chaperone protein HSC70, and HSC70 mediates the entry of USP9X into lysosomes for degradation.

[0023] The amino acid sequence of the polypeptide P7 provided by the present application is YGRKKRRQRRR-DLKRQ, which is a cell-penetrating peptide coupled with the KFERQ sequence after acetylation of the 2414th site of USP9X, can promote the absorption of cells to the polypeptide, and competitively inhibit the recognition of acetylated USP9X by HSC70.

[0024] The polypeptide of the present application has the function of inhibiting the inflammatory response of macrophages after myocardial infarction, and the polypeptide can inhibit the degradation of USP9X in macrophages after myocardial infarction, thereby inhibiting the inflammatory response of macrophages and effectively reducing pathological remodeling after myocardial infarction. Secondly, the polypeptide of the present application can enter target cells without obvious toxic side effects in an effective dose range.

[0025] The present application has the following beneficial effects:

[0026] (1) The polypeptide of the present application can enter macrophages, competitively inhibit the recognition of molecular chaperone HSC70 to USP9X, reduce the degradation of USP9X in inflammatory response, and has no obvious toxic side effects in the effective dose range; can effectively inhibit the inflammatory response of macrophages, thereby improving the pathological remodeling after myocardial infarction.

[0027] (2) The present application provides a new drug and scheme for the clinical treatment of ischemic heart disease, which is of great significance to improve the clinical treatment effect of ischemic heart disease and improve the quality of life of patients. BRIEF DESCRIPTION OF DRAWINGS

[0028] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed in the embodiments will be briefly introduced as follows.

[0029] Figure 1 Figure 1 is the expression change of USP9X in cardiac macrophages after myocardial infarction and its effect; wherein A is the flow detection of the expression change of USP9X in cardiac macrophages at different time points after myocardial infarction, and B is the qPCR result of the expression of inflammatory related genes of macrophages promoted by USP9X knockout;

[0030] Figure 2 Figure 2 is the effect of USP9X knockout in macrophages on cardiac fibrosis and cardiac function after myocardial infarction; wherein A is the representative graph of Sirius red staining of myocardial infarction section of mice with USP9X knockout in macrophages; B is the change of cardiac function after myocardial infarction of mice with USP9X knockout in macrophages;

[0031] Figure 3 Figure 3 is the mechanism of down-regulation of USP9X in inflammatory response after myocardial infarction; wherein A shows that the degradation of USP9X in macrophages can be blocked by knocking down HSC70 under inflammatory conditions; B suggests that the interaction of USP9X in macrophages with HSC70 increases under inflammatory conditions; C is the predicted potential KFERQ-like sequence of classical / activatable modified USP9X; D is the result of increased acetylation level of USP9X in inflammatory response;

[0032] Figure 4 Figure 4 is the polypeptide sequence capable of inhibiting the degradation of USP9X in macrophage inflammatory response; wherein A is a polypeptide sequence capable of competing with the KFERQ-like sequence of acetylation activated USP9X to bind to HSC70, and all polypeptides will be coupled with cell penetrating peptide YGRKKRRQRRR in N section to promote the absorption of polypeptides by cells; B is the screening result of polypeptide P7 inhibiting the degradation of USP9X;

[0033] Figure 5 Figure 5 is the HPLC purification result of polypeptide P7;

[0034] Figure 6Mass spectrum identification result of polypeptide P7;

[0035] Figure 7 Effect of polypeptide P7 on in-vitro HSC70 binding: A is a picture of polypeptide P7 with Rhodamine B fluorescence label enriched in primary mouse macrophages and co-localized with HSC70; B is an in-vitro verification result of polypeptide P7 competing with USP9X to bind HSC70;

[0036] Figure 8 Effect of polypeptide P7 on in-vivo inhibition of USP9X degradation; wherein, A is a flow cytometry result of polypeptide P7 inhibiting USP9X degradation in macrophages on the third day after myocardial infarction; B is a result of polypeptide P7 reducing inflammatory gene expression after myocardial infarction;

[0037] Figure 9 Improvement of cardiac fibrosis and cardiac function of a myocardial infarction mouse after intraperitoneal injection of polypeptide P7 every 2 days; wherein, A is a representative picture of Sirius red staining of a heart after polypeptide P7 injection; B is an improvement of cardiac function after polypeptide P7 injection;

[0038] Figure 10 Toxic and side effects evaluation of polypeptide P7 on mice; wherein, A is a picture of morphological changes of liver, kidney and small intestine; B is an influence of polypeptide treatment on serum glutamic-pyruvic transaminase (ALT), glutamic-oxalacetic transaminase (AST), urea nitrogen (BUN) and creatinine (Cr); DETAILED DESCRIPTION

[0039] The application provides application of a heart macrophage USP9X to preparation of a drug for treating ischemic heart disease as an intervention target.

[0040] The application also provides a polypeptide P7, and an amino acid sequence of the polypeptide P7 is (SEQ ID No. 1): YGRKKRRQRRR-DLKRQ. The application does not have special limitation to a preparation method of the polypeptide P7, and a person skilled in the art can synthesize according to a conventional polypeptide synthesis method. In the application, the YGRKKRRQRRR promotes cell absorption of the polypeptide, the DLKRQ simulates a KFERQ-like sequence formed after acetylation of a DLKRK fragment of USP9X, can competitively inhibit recognition of HSC70 to the sequence, and reduces autophagic degradation of USP9X.

[0041] The application also provides application of the polypeptide P7 in the above technical solution to preparation of a drug for inhibiting degradation of a heart macrophage USP9X. In the application, the polypeptide P7 preferably inhibits degradation of a heart macrophage USP9X after myocardial infarction.

[0042] This invention also provides the application of the peptide P7 described in the above technical solution in the preparation of a drug that reduces the binding of cardiac macrophages USP9X and HSC70.

[0043] The present invention also provides the application of the polypeptide P7 described in the above technical solution in the preparation of drugs for treating ischemic heart disease.

[0044] This invention also provides a medicament for treating ischemic heart disease, comprising the polypeptide P7 described in the above-described technical solution. In this invention, the medicament preferably includes a pharmaceutically acceptable carrier and / or excipient. In this invention, the medicament is preferably a pharmaceutical preparation administered by injection, oral administration, nasal mucosa, lung administration, rectal administration, oral mucosa administration, or skin administration. In this invention, the injection preferably includes intramyocardial injection, intradermal injection, subcutaneous injection, intramuscular injection, or intravenous injection.

[0045] To further illustrate the present invention, the following detailed description is provided in conjunction with embodiments, but these should not be construed as limiting the scope of protection of the present invention.

[0046] Example 1

[0047] Changes in the expression and function of USP9X in cardiac macrophages after myocardial infarction

[0048] Wild-type mice underwent myocardial infarction surgery. The mice's hearts were digested on days 0, 3, and 7 post-infarction. Flow cytometry analysis was used to analyze the expression of USP9X in cardiac macrophages. Figure 1 The study showed that the expression of USP9X in mouse cardiac macrophages decreased in the first 3 days after myocardial infarction and rebounded on day 7, demonstrating that macrophage USP9X plays a role in the inflammatory response after myocardial infarction.

[0049] Bone marrow was isolated from USP9X myeloid knockout mice and their littermate control mice, and induced with 10 ng / ml M-CSF for 7 days. The expression of pro-inflammatory and anti-inflammatory genes in macrophages after TLR4 activation was observed. Figure 1 The results showed that, after stimulation with LPS (an agonist of TLR4), inhibition of USP9X promoted the expression of pro-inflammatory genes (including Il1b, Il6, and Nos2) and attenuated the expression of anti-inflammatory genes Arg1 and Il10.

[0050] Example 2

[0051] Effects of macrophage USP9X knockout on cardiac fibrosis and cardiac function after myocardial infarction

[0052] Get 8 weeks of USP9X flox / flox USP9X flox / flox LysM creMice were subjected to myocardial infarction modeling, and then randomly divided into two groups, 10 in each group. Before modeling, 3 days after modeling, the cardiac ultrasound systolic function evaluation was performed to ensure that there was no difference in the baseline cardiac function of the two groups. Then, 7 days, 14 days and 28 days after myocardial infarction, ultrasound was performed. After 28 days, the sample was taken, such as Figure 2 As shown in FIG. 2A, it is a representative Sirius red staining diagram of each layer of the heart of the two groups of mice. It can be seen that the area of the infarct fibrosis region of the USP9X macrophage knockout group is larger than that of the control group.

[0053] As shown in FIG. 2B, at 7, 14 and 28 days after myocardial infarction, the left ventricular ejection fraction of the USP9X macrophage knockout group was lower than that of the control group, and there was a statistical difference, indicating that the left ventricular cardiac function of the heart was worse. Figure 2

[0054] Example 3

[0055] Mechanism of USP9X down-regulation in inflammatory response after myocardial infarction

[0056] Hspa8 (HSC70) is a key molecule of chaperone-mediated autophagy, which can recognize the KFERQ sequence of the target substrate, form a chaperone-protein complex, and the complex is delivered to the lysosome for degradation. Bone marrow-derived macrophages were divided into three groups, one group was not treated, and the other two groups were given LPS stimulation, and one of the two groups was knocked down HSC70, as shown in FIG. 3A. Figure 3 As shown in FIG. 3A, knocking down HSC70 can inhibit the degradation of USP9X in the inflammatory response.

[0057] Total protein of LPS-treated or untreated macrophages was extracted and subjected to immunoprecipitation using an antibody against HSC70, as shown in FIG. 3B. Figure 3 As shown in FIG. 3B, the binding of USP9X and HSC70 increases in the inflammatory response.

[0058] ​Proteins that can be recognized by HSC70 generally have a KFERQ sequence. The characteristics of a KFERQ sequence are: (1) glutamine (Q) flanking it; (2) one or two positively charged amino acids, such as lysine (K) and arginine (R); (3) one or two hydrophobic amino acids, such as leucine (L), isoleucine (I), valine (V) or phenylalanine (F); and (4) negatively charged amino acids, such as glutamic acid (E) and aspartic acid (D). Proteins can also produce KFERQ-like sequences through post-translational modifications. For example, phosphorylation of serine (S), threonine (T), or tyrosine (Y) is similar to that of negatively charged amino acids; the properties of acetylated lysine (K) are similar to those of glutamine (Q), etc. KFERQ finder software v0.8 predicted the presence of KFERQ sequences in USP9X, including two classic KFERQ sequences, seven acetylation-activated KFERQ-like sequences, and three phosphorylation-activated KFERQ-like sequences (e.g., KFERQ finder software v0.8). Figure 3 (As shown in C).

[0059] Total protein was extracted from LPS-treated or untreated macrophages and immunoprecipitated using a USP9X antibody, such as... Figure 3 As shown in Figure D, acetylation of USP9X increases during the inflammatory response, while phosphorylation remains unchanged, suggesting that USP9X acetylation may produce a KFERQ-like sequence that can be recognized by HSC70, thereby increasing the autophagic degradation of USP9X.

[0060] Example 4

[0061] Screening of peptides: such as Figure 4 As shown in Figure A, seven KFERQ-like sequences on USP9X that can be activated by acetylation were synthesized into peptides, enabling them to compete with acetylated USP9X and inhibit HSC70 binding and degradation of USP9X. To further increase the cell permeability of the peptides and allow them to enter cells and exert their effects, this invention further optimized the design of these peptide sequences, namely, the N-terminal membrane-penetrating peptide YGRKKRRQRRR. Mouse bone marrow-derived macrophages were isolated and treated with LPS while simultaneously being treated with the aforementioned seven peptides, as follows... Figure 4 As shown in Figure B, the peptide P7, namely YGRKKRRQRRR-DLKRQ, can inhibit LPS-mediated degradation of USP9X, demonstrating that under inflammatory activation, the 2414 site of macrophage USP9X can be acetylated to produce a KFERQ-like sequence, which is recognized by HSC70 and degraded. The peptide DLKRQ can competitively inhibit the degradation of USP9X.

[0062] Example 5

[0063] HPLC purification results and mass spectrometry (MS) identification results of peptide P7

[0064] The polypeptide was synthesized by using the conventional polypeptide synthesis method in the art, and purified and identified by high performance liquid chromatography (HPLC) and mass spectrometry (MS). The results are shown in Table 1 and Table 2, respectively. Figure 5 , 6 After purification by high performance liquid chromatography (HPLC), the purity of the sample was detected to be 97.41%, and the mass spectrometry (MS) identification was correct, and the molecular weight was 2200.5.

[0065] Example 6

[0066] Effect of polypeptide P7 on entering target cells and binding to HSC70

[0067] Mouse bone marrow-derived macrophages were isolated, and the experimental group was added with polypeptide P7 labeled with Rhodamine B fluorescent marker in the culture medium (the final concentration of the polypeptide was 20 μM), and the control group was only added with normal saline. Both were cultured for 2 hours. The culture supernatant was discarded, washed twice with PBS buffer, fixed with 4% paraformaldehyde at room temperature for 10 minutes, and then subjected to membrane permeation and blocking, and then incubated with HSC70 primary antibody overnight. The next day, the cells were washed with PBS buffer for 3 times, and then incubated with fluorescent secondary antibody at room temperature for 1 hour. After washing away the secondary antibody, the cells were sealed with sealing agent containing DAPI nuclear dye, and then observed and photographed under a laser confocal microscope. As shown in FIG. 6A, in the control group, only the morphology of the cell nucleus with positive blue DAPI nuclear dye and green HSC70 could be observed, and in the group with the polypeptide labeled with fluorescent marker, significant red Rhodamine B fluorescent signal could be observed in the macrophages and co-localized with HSC70. This indicates that only 2 hours of co-culture is needed, and the polypeptide can penetrate the cell membrane, enter the target cells, and bind to HSC70. Figure 7

[0068] Mouse bone marrow-derived macrophages were isolated and randomly divided into four groups. One group was not treated, and the other three groups were stimulated with LPS. At the same time, two of the three groups were treated with control peptide or polypeptide P7, respectively. After 24 hours, the cells were collected and subjected to immunoprecipitation with USP9X antibody. As shown in FIG. 6B, polypeptide P7 but not control peptide can reduce the binding of USP9X to HSC70. Figure 7

[0069] Example 7

[0070] Effect of polypeptide P7 on inhibiting USP9X degradation in vivo

[0071] Eight-week-old C57 mice were subjected to heart infarction operation or sham operation, and then randomly divided into two groups, with 5 mice in each group. One group was given intraperitoneal injection of polypeptide P7 (20 mg / kg) after modeling, and the control group was given the same dose of control peptide injection. Three days later, the samples were taken, and the heart was digested for flow analysis of USP9X expression in heart macrophages, as shown in FIG. 7. Figure 8 ​​Figure 6A shows that the inhibitory part of USP9X is reversed after injection of polypeptide P7 in mice with myocardial infarction.

[0072] Eight-week-old C57 mice were subjected to myocardial infarction surgery and then randomly divided into three groups, two of which were given injection of control peptide or polypeptide P7, as shown in Figure 7A. Figure 8 Figure 6B shows that polypeptide P7, but not control peptide, can effectively reduce the expression of inflammatory genes (Il l, Il6, Nos2, Tnf, Ccl2) and increase the expression of anti-inflammatory genes (Argl) in the heart 3 days after myocardial infarction.

[0073] Example 8

[0074] Evaluation of cardiac fibrosis and cardiac function in mice with myocardial infarction after injection of polypeptide P7

[0075] Eight-week-old C57 mice were subjected to myocardial infarction surgery and then randomly divided into three groups, two of which were given injection of control peptide or polypeptide P7, as shown in Figure 7A.

[0076] Figure 6A shows that the inhibitory part of USP9X is reversed after injection of polypeptide P7 in mice with myocardial infarction. Figure 9 Figure 6A shows that the inhibitory part of USP9X is reversed after injection of polypeptide P7 in mice with myocardial infarction.

[0077] Figure 6B shows that polypeptide P7, but not control peptide, can effectively reduce the expression of inflammatory genes (Il l, Il6, Nos2, Tnf, Ccl2) and increase the expression of anti-inflammatory genes (Argl) in the heart 3 days after myocardial infarction. Figure 9 Figure 6B shows that polypeptide P7, but not control peptide, can effectively reduce the expression of inflammatory genes (Il l, Il6, Nos2, Tnf, Ccl2) and increase the expression of anti-inflammatory genes (Argl) in the heart 3 days after myocardial infarction.

[0078] Example 9

[0079] Evaluation of the toxic side effects of polypeptide P7 on mice by HE staining and blood biochemical tests

[0080] At the time of taking the mice of embodiment 8, which were made 28 days after the middle cerebral artery occlusion and completed the polypeptide treatment, the kidney, liver and small intestine of the mice were taken, fixed and dehydrated, and then embedded to make paraffin sections with a thickness of 4 microns. After the sections were deparaffinated, HE staining was performed using a full-automatic staining machine, and neutral gum was used for sealing the sections, and then the sections were photographed using a Leica upright microscope. At the same time, the blood of the mice was collected into 1.5ml EP tubes, and after being placed at room temperature for 2 hours, the blood was allowed to coagulate at 4℃, 3000rpm, and centrifuged for 10min to obtain the upper serum, and ELISA was used to determine the levels of creatinine (Cr), urea nitrogen (BUN), glutamic-pyruvic transaminase (ALT) and glutamic-oxalacetic transaminase (AST).

[0081] As shown in Figure 10 The liver, kidney and small intestine of the control peptide, polypeptide P7 treatment group and control group mice showed no pathological changes (such as vacuolar degeneration, pigment deposition, cell necrosis and inflammatory cell infiltration), indicating that the polypeptide P7 had no obvious toxic side effects on the mice at an effective treatment dose, and had good biological safety.

[0082] As shown in Figure 10 As shown in B, the values of creatinine (Cr), urea nitrogen (BUN), serum glutamic-pyruvic transaminase (ALT) and serum glutamic-oxalacetic transaminase (AST) of the control peptide, polypeptide P7 treatment group and control group mice showed no significant difference. It is indicated that the polypeptide P7 has no effect on the liver and kidney function of the mice at an effective treatment dose, and has good biological safety.

[0083] The present application relates to the field of biological medicine, and discloses a polypeptide and application thereof in preparation of a drug for treating ischemic heart disease. The amino acid sequence of the polypeptide is YGRKKRRQRRR-DLKRQ. The polypeptide has good cell penetration and no obvious toxic side effects in an effective dose range; can effectively inhibit the degradation of USP9X in macrophages after myocardial infarction, thereby inhibiting the inflammatory response of the heart, effectively inhibiting cardiac fibrosis and improving the heart function. The present application provides a new drug and scheme for the clinical treatment of ischemic heart disease, and has important significance for improving the life quality of patients.

[0084] Although the above embodiment has made a detailed description of the present application, it is only a part of the embodiments of the present application, but not all the embodiments, and other embodiments can be obtained by people under the premise of no creativity according to the present embodiment, which all belong to the protection scope of the present application.

Claims

1. A polypeptide P7, characterized in that, The amino acid sequence of the polypeptide P7 is YGRKKRRQRRR - DLKRQ.

2. The use of the polypeptide P7 according to claim 1 in the preparation of drugs for treating myocardial infarction.

3. A drug for treating myocardial infarction, comprising the polypeptide P7 of claim 1.

4. The drug according to claim 3, characterized in that, The drug also includes pharmaceutically acceptable carriers and / or excipients.

5. The drug according to claim 3, characterized in that, The drug is a pharmaceutical preparation that can be administered by injection, oral administration, nasal mucosa, lung, rectum, oral mucosa, or skin.

6. The drug according to claim 5, characterized in that, The injection includes intramyocardial injection, intradermal injection, subcutaneous injection, intramuscular injection, or intravenous injection.

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