Use of PCBP2 overexpression vector for preparing miri therapeutic drugs

Abstract

The application belongs to the technical field of biological medicine, and particularly relates to application of PCBP2 overexpression vector in preparation of MIRI treatment drugs. In order to solve the problem of lack of effective anti-apoptosis target points in treatment of apoptosis dominant myocardial ischemia reperfusion injury, the application provides application of the PCBP2 overexpression vector in preparation of the MIRI treatment drugs. The endogenous protein PCBP2 down-regulated in ischemia reperfusion injury is precisely up-regulated through the overexpression vector, and myocardial cell apoptosis balance is efficiently regulated. The anti-apoptosis protein Bcl-2 is significantly up-regulated, the pro-apoptosis protein Bax is down-regulated, the myocardial cell apoptosis rate is directly reduced, and the myocardial cell excessive apoptosis process under the apoptosis dominant injury scenario is blocked from a molecular level. The application simultaneously realizes double protection of myocardial structure and function, can not only improve heart function, but also reduce myocardial infarction area, and provides a new candidate strategy for anti-apoptosis treatment of the apoptosis dominant myocardial ischemia reperfusion injury.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, and in particular relates to the application of PCBP2 overexpression vector in the preparation of MIRI therapeutic drugs. Background Technology

[0002] Myocardial ischemia-reperfusion injury (MIRI) is a key complication of myocardial infarction during reperfusion therapy, and its core pathological feature is abnormal cardiomyocyte death. Based on the dominant mode of cell death, MIRI can be clearly divided into two subtypes with distinct mechanisms: apoptosis-dominated and ferroptosis-dominated, which differ fundamentally in pathological characteristics, regulatory pathways, and treatment requirements.

[0003] The core characteristic of apoptosis-dominant myocardial ischemia-reperfusion injury is that cardiomyocytes die primarily through apoptosis. Oxidative stress accumulates slowly during the pathological process, and apoptotic pathways are continuously activated, a feature particularly pronounced in the ischemic borderline zone. This type of injury often occurs after mild to moderate ischemia, with a slow or prolonged reperfusion process. The molecular mechanism relies on apoptosis-specific regulatory pathways, primarily involving caspase family protease activation and Bcl-2 / Bax apoptosis imbalance. Therefore, treatment should focus on targeted inhibition of apoptosis pathways, blocking excessive cardiomyocyte death by regulating apoptosis-related molecules.

[0004] Ferroprelation-dominated myocardial ischemia-reperfusion injury is characterized by ferroptosis as the primary mode of cell death. Its pathological mechanism is closely related to iron overload and oxidative stress, with the ischemic core region being the main area of ​​occurrence. This type of injury commonly occurs after severe ischemia, with rapid restoration of blood flow during reperfusion. The core regulatory pathways revolve around iron metabolism and lipid peroxidation, relying heavily on ferroptosis-specific molecular mechanisms such as GPX4 antioxidant activity and SLC7A11-mediated glutathione synthesis. Treatment requires targeted regulation of iron homeostasis and lipid peroxidation processes to inhibit ferroptosis-related cell damage.

[0005] Poly(RC) Binding Protein 2 (PCBP2) is an RNA-binding protein known to focus on RNA metabolism regulation, cellular iron homeostasis maintenance, and cGAS-STING immune pathway regulation. It is centrally involved in physiological and pathological processes such as viral replication, cellular senescence, and ferroptosis. Previous studies have confirmed that PCBP2 can act as a target protein of tsACC, regulating ferroptosis by stabilizing SLC7A11 mRNA and inhibiting Ptgs2 expression. However, these studies are limited to ferroptosis-dominated MIRIs and have not explored any association between PCBP2 and apoptosis pathways, nor its role in apoptosis-dominated MIRIs.

[0006] Since apoptosis and ferroptosis are completely independent cell death mechanisms with no overlap in their core regulatory pathways, key molecules, and pathological characteristics, the inhibitory function of PCBP2 in ferroptosis cannot be extrapolated to the treatment of apoptosis-dominant myocardial ischemia-reperfusion injury (MIRI). Currently, there is still a lack of effective targets for apoptosis-inhibiting therapies targeting apoptosis-dominant myocardial ischemia-reperfusion injury. Summary of the Invention

[0007] To address the lack of effective anti-apoptotic targets in the treatment of apoptosis-dominant myocardial ischemia-reperfusion injury, this invention provides the application of PCBP2 overexpression vectors in the preparation of MIRI therapeutic drugs.

[0008] The technical solution of the present invention: Application of PCBP2 overexpression vector in the preparation of drugs for the treatment of myocardial ischemia-reperfusion injury, wherein MIRI is apoptosis-dominant myocardial ischemia-reperfusion injury, and the nucleotide sequence encoding PCBP2 is shown in SEQ ID NO.1.

[0009] Furthermore, the PCBP2 overexpression vector is an adeno-associated virus vector AAV9-PCBP2 that overexpresses the PCBP2 gene, containing a nucleotide sequence encoding PCBP2 and a myocardial-specific promoter; the myocardial-specific promoter is the cardiac troponin T promoter.

[0010] Furthermore, the MIRI treatment drug is in the form of an intravenous injection.

[0011] Furthermore, the drug for treating myocardial ischemia-reperfusion injury has at least one of the following uses: (1) Restore the balance between pro-apoptotic protein Bax and anti-apoptotic protein Bcl2 after reperfusion and reduce cardiomyocyte apoptosis; (2) Reduce the area of ​​myocardial infarction after reperfusion; (3) Improve cardiac function after reperfusion.

[0012] The beneficial effects of this invention are: This invention is the first to discover that PCBP2 can serve as an effective anti-apoptotic target for apoptosis-dominant myocardial ischemia-reperfusion injury, providing a novel direction for the treatment of this specific subtype of injury. By precisely upregulating the endogenous protein PCBP2, which is downregulated in ischemia-reperfusion injury, through an overexpression vector, it avoids the need for exogenous drugs, effectively circumventing non-specific side effects and achieving targeted intervention on myocardial tissue. Its core advantage lies in efficiently regulating the balance of cardiomyocyte apoptosis: by significantly upregulating the anti-apoptotic protein Bcl-2 and downregulating the pro-apoptotic protein Bax, it directly reduces the apoptosis rate of cardiomyocytes, blocking the excessive apoptosis process of cardiomyocytes in apoptosis-dominant injury scenario at the molecular level. Furthermore, it achieves dual protection of myocardial structure and function, not only improving key cardiac function indicators such as ejection fraction and fractional shortening, but also reducing the levels of injury markers such as peripheral blood CK-MB and LDH and shrinking the myocardial infarction area. Moreover, the overexpression vector is easy to operate, highly targeted, and has a clear mechanism of action directly targeting apoptosis regulation, providing a new candidate strategy for anti-apoptotic treatment of apoptosis-dominant myocardial ischemia-reperfusion injury, and possesses high clinical translational and application value. Attached Figure Description

[0013] Figure 1 The image shows a comparison of Western Blot results of PCBP2 in the myocardial tissue of mice in the control group and the ischemia-reperfusion (IR) group in Example 1. A is a Western Blot result image, and B is a comparison of PCBP2 protein expression levels.

[0014] Figure 2 The image shows a comparison of the Western Blot results of PCBP2 in the myocardial tissue of mice in the control group and H2O2 group in Example 1. A is the Western Blot result image, and B is a comparison of the expression level of PCBP2 protein.

[0015] Figure 3 This is a comparison of PCBP2 mRNA expression levels in the myocardial tissue of mice in the control group and H2O2 group in Example 1.

[0016] Figure 4 Echocardiograms of four groups of mice in Example 2: A is the control group, B is the ischemia-reperfusion injury group, C is the PCBP2 overexpression + ischemia-reperfusion injury group, and D is the control virus + ischemia-reperfusion injury group.

[0017] Figure 5 This is a comparison chart of cardiac ejection fraction and fractional shortening of four groups of mice in Example 2. A represents ejection fraction, and B represents fractional shortening.

[0018] Figure 6 This is a comparison chart of CK-MB and LDH levels in the blood pressure of four groups of mice in Example 3. A represents CK-MB, and B represents LDH.

[0019] Figure 7 The image shows a comparison of TTC staining of heart sections from mice in Example 3, specifically the PCBP2 overexpression + ischemia-reperfusion injury group and the control virus + ischemia-reperfusion injury group. A represents the control virus + ischemia-reperfusion injury group, and B represents the PCBP2 overexpression + ischemia-reperfusion injury group.

[0020] Figure 8 This is a comparison of the myocardial infarction area in mice in Example 3, specifically the group overexpressing PCBP2+ ischemia-reperfusion injury and the control virus+ ischemia-reperfusion injury group.

[0021] Figure 9 The image shows a comparison of TUNEL staining results of four groups of mouse myocardial tissue in Example 4. A is the control group, B is the ischemia-reperfusion injury group, C is the PCBP2 overexpression + ischemia-reperfusion injury group, and D is the control virus + ischemia-reperfusion injury group.

[0022] Figure 10 This is a comparison of the number of TUNEL-positive cells in the myocardial tissue of four groups of mice in Example 4;

[0023] Figure 11 This is a comparison of Bcl2 protein expression levels in four groups of mouse cardiomyocytes in Example 4. A is a Western Blot result, and B is a comparison of Bcl2 protein expression levels.

[0024] Figure 12 The figures show a comparison of Bax protein expression levels in four groups of mouse cardiomyocytes in Example 4. A is a Western Blot result, and B is a comparison of Bax protein expression levels. Detailed Implementation

[0025] The technical solution of the present invention will be further described below with reference to embodiments, but it is not limited thereto. Any modifications or equivalent substitutions to the technical solution of the present invention without departing from the spirit and scope of the technical solution of the present invention should be covered within the protection scope of the present invention. In the following embodiments, the process equipment or apparatus not specifically specified are all conventional equipment or apparatus in the art. Unless otherwise specified, the raw materials used in the embodiments of the present invention are all commercially available; unless otherwise specified, the technical means used in the embodiments of the present invention are all conventional means well known to those skilled in the art.

[0026] Example 1

[0027] This example demonstrates that PCBP2 expression is reduced in myocardial tissue after myocardial ischemia-reperfusion.

[0028] I. Methods for grouping experimental animals and establishing experimental models:

[0029] Eight-week-old male C57BL / 6J mice (weighing 22-25g) were randomly divided into two groups:

[0030] (1) Control group: only open-chest surgery and suture threading were performed, without ligation of the coronary arteries;

[0031] (2) Ischemia-reperfusion injury group: Blood flow was restored 45 minutes after ligation of the left anterior descending coronary artery, and reperfusion was performed for 24 hours.

[0032] 2. Mice in the control group and the ischemia-reperfusion injury group were sacrificed 24 hours after surgery and 24 hours after reperfusion. The heart was quickly removed, the left ventricular myocardium was separated along the interventricular septum, and the right ventricle and atrium were removed on ice. The expression of PCBP2 in the myocardial tissue was detected.

[0033] (1) Western Blot detection:

[0034] 1. Protein extraction: Homogenize left ventricular myocardial tissue with RIPA lysis buffer (containing PMSF), centrifuge at 13500 rpm for 15 minutes, and collect the supernatant;

[0035] 2. Electrophoretic transfer: Proteins were separated by 10% SDS-PAGE and transferred to an NC membrane;

[0036] 3. Antibody incubation: anti-PCBP2 antibody (1:1000, Abclonal), anti-β-actin antibody (1:1000, Affinity).

[0037] 4. Results Analysis: Image J quantifies grayscale values, and the PCBP2 / β-actin ratio represents the relative expression level.

[0038] The results are as follows Figure 1 As shown, compared with the control group, the expression of PCBP2 protein in the myocardial tissue of mice in the ischemia-reperfusion injury group was significantly reduced (P<0.05).

[0039] III. Using the H2O2-induced oxidative stress injury cell model construction method, mouse primary cardiomyocytes were treated to further confirm that PCBP2 expression was downregulated in mouse cardiomyocytes after ischemia-reperfusion.

[0040] The specific procedures are as follows: Primary cardiomyocytes in the logarithmic growth phase of mice were taken, and after adjusting the cell density, they were seeded into culture plates. When the cells adhered and fused to 70%~80%, they were incubated in serum-free medium containing different concentration gradients of H2O2 for 24 h. At the same time, a blank control group (containing only serum-free medium) was set up. The protein and mRNA expression levels of PCBP2 in the two groups of cells were detected by Western Blot and qRT-PCR to verify the expression change of PCBP2 under ischemia-reperfusion injury-related oxidative stress.

[0041] Western blotting results are as follows: Figure 2 As shown, compared with the control group, the relative expression level of PCBP2 protein in the H2O2-treated group was significantly lower than that in the control group (p<0.0001), indicating that H2O2-induced oxidative stress downregulates the protein expression of PCBP2 in cardiomyocytes.

[0042] (2) qRT-PCR detection:

[0043] 1. RNA extraction: Total RNA was extracted from the left ventricle using the Trizol method and quantified using NanoDrop.

[0044] 2. Reverse transcription: 1 μg of RNA was used to synthesize cDNA using the PrimeScript RT kit;

[0045] 3. Quantitative PCR: SYBR Green assay for PCBP2 mRNA detection.

[0046] 4. Results Analysis: 2 -ΔΔCt The relative expression level is calculated using this method.

[0047] The results are as follows Figure 3 As shown, the relative expression level of PCBP2 mRNA in the H2O2-treated group was also significantly lower than that in the control group (p<0.0001), suggesting that this downregulation may have already occurred at the transcriptional level.

[0048] In the H2O2-based oxidative stress cell model, the expression of both PCBP2 protein and mRNA was significantly reduced, validating the conclusion that PCBP2 expression is downregulated in mouse cardiomyocytes after ischemia-reperfusion.

[0049] Example 2

[0050] This embodiment demonstrates that overexpression of PCBP2 can improve cardiac function after ischemia-reperfusion.

[0051] I. Construction of overexpression vectors

[0052] (1) Carrier selection:

[0053] This embodiment uses an adeno-associated virus type 9 (AAV9) vector system with a vector backbone of ssAAV-cTnT-PCBP2-SV40pA, containing the following elements: cardiac troponin T (cTnT) promoter, target gene PCBP2 coding sequence, and SV40pA which helps improve expression efficiency and stability. The nucleotide sequence encoding PCBP2 is shown in SEQ ID NO.1.

[0054] (2) PCBP2 gene cloning and viral packaging

[0055] PCBP2 gene cloning and viral packaging were performed by Shanghai Jikai Gene Biotechnology Co., Ltd. using a gene cloning-viral packaging-purification and concentration method, yielding purified AAV9-PCBP2 viral particles with a titer of 1×10⁻⁶. 13 vg / mL.

[0056] (3) Control virus

[0057] The PCBP2 sequence was replaced with a meaningless sequence, while the remaining elements were completely identical to AAV9-PCBP2. The process was completed by Shanghai Jikai Gene Biotechnology Co., Ltd. using a gene cloning-virus packaging-purification and concentration method to obtain purified AAV9-NC virus particles with a titer of 1×10⁻⁶. 13 vg / mL.

[0058] II. Animal Experiment Grouping and Model Establishment Methods:

[0059] Eight-week-old male C57BL / 6J mice (weighing 22-25g) were randomly divided into four groups:

[0060] (1) Control group: The same amount of normal saline was injected into the tail vein, and the left anterior descending coronary artery was opened but not ligated;

[0061] (2) Ischemia-reperfusion injury group: equal volume of normal saline was injected into the tail vein. After 4 weeks, the left anterior descending coronary artery was ligated for 45 minutes and blood flow was restored. Reperfusion was performed for 24 hours.

[0062] (3) Overexpression of PCBP2 + ischemia-reperfusion injury group: AAV9-PCBP2 (100μL, 1×10) was injected into the tail vein. 11 (vg), blood flow was restored 45 minutes after ligation of the left anterior descending coronary artery 4 weeks later, followed by reperfusion for 24 hours;

[0063] (4) Control group of virus + ischemia-reperfusion injury: AAV9-NC (100μL, 1×10) was injected into the tail vein. 11 (vg), blood flow was restored 45 minutes after ligation of the left anterior descending coronary artery 4 weeks later, followed by reperfusion for 24 hours;

[0064] 3. Monitor cardiac function through echocardiography.

[0065] Echocardiograms of the four groups of mice are as follows: Figure 4 As shown, the myocardial tissue in the control group showed clear ultrasound layering and regular structure, reflecting the morphological characteristics of normal myocardium; the myocardial layer in the ischemia-reperfusion injury group showed disordered texture and blurred layering, indicating that ischemia-reperfusion caused myocardial structural damage; the regularity of the myocardial structure in the PCBP2+ ischemia-reperfusion injury group was significantly better than that in the ischemia-reperfusion injury group alone, and was close to the state of the control group.

[0066] The cardiac ejection fraction and fractional shortening of the four groups of mice were compared to, for example... Figure 5 As shown, the ejection fraction in the ischemia-reperfusion injury group was significantly lower than that in the control group (p<0.0001); after overexpression of PCBP2, the ejection fraction significantly increased; the trend of the fractional shortening was consistent with that of the ejection fraction: it was significantly reduced in the ischemia-reperfusion injury group and significantly increased after overexpression of PCBP2. This indicates that overexpression of PCBP2 can effectively alleviate myocardial structural damage caused by ischemia-reperfusion and significantly improve cardiac function. Its mechanism of action may be related to PCBP2's inhibition of cardiomyocyte apoptosis and reduction of oxidative stress damage, providing a new potential target and experimental evidence for the clinical treatment of MIRI.

[0067] Example 3

[0068] This embodiment demonstrates that overexpression of PCBP2 can reverse myocardial damage caused by ischemia-reperfusion and reduce the infarct area.

[0069] I. Detection of CK-MB and LDH levels in blood

[0070] CK-MB (creatine kinase isoenzyme) is mainly found in cardiomyocytes and is a specific biochemical marker of myocardial injury; LDH (lactate dehydrogenase) is present in high amounts in cardiomyocytes and is a sensitive marker reflecting the degree of cardiomyocyte damage. When cardiomyocytes are damaged / necrotized, the cell membrane integrity is disrupted, and intracellular CK-MB and LDH are released into the bloodstream. The larger the infarct area and the more cardiomyocytes die, the higher the levels of these two substances in the blood. In this example, based on the animal experiment grouping and model establishment in Example 2, peripheral blood was collected from mice in each group. After centrifugation to separate serum / plasma, the concentrations of CK-MB and LDH were detected using CK-MB and LDH kits.

[0071] The results are as follows Figure 6 As shown, the creatine kinase isoenzyme level in the ischemia-reperfusion injury group was significantly higher than that in the control group (p<0.0001), indicating cardiomyocyte damage and massive release of the enzyme into the blood. The level of this enzyme was significantly reduced in the PCBP2 overexpression + ischemia-reperfusion injury group. The trend of lactate dehydrogenase was consistent with that of creatine kinase isoenzyme, and the level of lactate dehydrogenase in the ischemia-reperfusion injury group was significantly increased (p<0.0001). After PCBP2 overexpression, the level of this enzyme decreased significantly.

[0072] This indicates that overexpression of PCBP2 can significantly reduce the release of myocardial injury markers induced by ischemia-reperfusion injury, suggesting that it can effectively reduce the degree of myocardial cell damage.

[0073] II. In order to examine the effect of PCBP2 overexpression on myocardial injury from the perspective of tissue morphology changes, this embodiment, based on the animal experimental grouping and model establishment in Example 2, performed TTC staining on heart sections of mice in the PCBP2 overexpression + ischemia-reperfusion injury group and the control virus + ischemia-reperfusion injury group.

[0074] After TTC staining, living myocardial tissue appeared red, while necrotic infarct areas appeared pale white; mouse TTC staining results were as follows. Figure 7 As shown, the quantified myocardial infarction area is compared to... Figure 8 As shown, the myocardial infarction area in the control virus + ischemia-reperfusion injury group was about 30%; while the infarction area in the PCBP2 overexpression + ischemia-reperfusion injury group was significantly reduced to only about 10%, and the difference between the two groups was statistically significant (p=0.0001).

[0075] Overexpression of PCBP2 can significantly reduce the area of ​​myocardial infarction caused by ischemia-reperfusion injury, further verifying its cardioprotective effect on MIRI.

[0076] Example 4

[0077] This embodiment demonstrates that overexpression of PCBP2 can reduce cardiomyocyte apoptosis after ischemia-reperfusion.

[0078] The Bcl-2 protein family is a core regulatory family of apoptosis, primarily regulating cell survival and death through interactions among its members. Pro-apoptotic protein Bax and anti-apoptotic protein Bcl2, as classic members of this family, regulate apoptosis via the mitochondrial pathway through their interactions, and are key regulatory molecules in the apoptotic process during myocardial ischemia-reperfusion injury. Under normal conditions, Bax and Bcl2 maintain a balance, sustaining cell survival; after myocardial ischemia-reperfusion, injury signals induce increased Bax expression and decreased Bcl2 expression, disrupting the Bax / Bcl2 balance and ultimately initiating the apoptotic program.

[0079] To investigate whether overexpression of PCBP2 reduces myocardial injury and decreases cardiomyocyte apoptosis, this example, based on the animal experiment grouping and model establishment in Example 2, detected apoptosis-related proteins in each group of mice.

[0080] I. TUNEL staining to detect cardiomyocyte apoptosis

[0081] Four groups of mouse myocardial tissue sections were fixed, permeabilized, and blocked. Terminal deoxynucleotidyl transferase (TdT) and fluorescently labeled dUTP were added for enzymatic labeling. Then, DAPI staining solution was added to label all cell nuclei, and the staining results were observed using a fluorescence microscope. The results of staining and comparison of the number of TUNEL-positive cells are shown below. Figure 9 and Figure 10As shown, red fluorescence represents TUNEL-labeled apoptotic cells, blue represents DAPI-labeled total cell nuclei, and green represents cardiac muscle structure markers.

[0082] Figure 9 The results showed that the control group had almost no red apoptotic signal and the cardiomyocyte structure was intact; the ischemia-reperfusion group had a significant increase in red apoptotic signal, indicating a significant increase in cardiomyocyte apoptosis; the ischemia-reperfusion group with PCBP2 overexpression had a significant decrease in red apoptotic signal, close to the level of the control group. Figure 10 The results also showed that the TUNEL-positive cell rate in the ischemia-reperfusion injury group was significantly higher than that in the control group (p<0.0001), indicating that ischemia-reperfusion significantly promoted cardiomyocyte apoptosis, suggesting that the ischemia-reperfusion model constructed in this experiment is an apoptosis-dominant type of myocardial ischemia-reperfusion injury; the TUNEL-positive cell rate in the PCBP2+ ischemia-reperfusion injury group was significantly reduced (p<0.0001).

[0083] This indicates that overexpression of PCBP2 can specifically inhibit excessive apoptosis of cardiomyocytes in apoptosis-dominant injury, which is one of the core mechanisms by which it exerts its cardioprotective effect.

[0084] II. Western blot analysis to detect the effect of PCBP2 overexpression on Bax / Bcl2.

[0085] Total protein was extracted from the myocardial tissue of mice in each group, and Western blot was used to detect the expression of BAX and Bal2 proteins. Results are as follows: Figure 11 and Figure 12 As shown, the relative expression level of Bcl-2 in the ischemia-reperfusion injury group was significantly lower than that in the control group (p<0.0001), while the relative expression level of Bax was significantly higher than that in the control group (p<0.0001). The apoptosis regulation balance of Bax / Bcl-2 was significantly disrupted, and this molecular characteristic is highly consistent with the pathological mechanism of apoptosis-dominant injury. In the ischemia-reperfusion injury group with overexpression of PCBP2, the Bcl-2 level was significantly increased and significantly higher than that in the simple injury group (p<0.0001), while the Bax level was significantly decreased and significantly lower than that in the simple injury group (p=0.004). The apoptosis regulation balance was effectively restored. The relative expression level of Bax in the ischemia-reperfusion injury group was significantly higher than that in the control group (p<0.0001).

[0086] The above results further confirm that the ischemia-reperfusion injury in this experiment is mainly characterized by apoptosis as the mode of cell death, belonging to the apoptosis-dominant type of myocardial ischemia-reperfusion injury. Overexpression of PCBP2 can precisely regulate the balance of apoptosis-related proteins by upregulating the expression of the anti-apoptotic protein Bcl-2 and downregulating the expression of the pro-apoptotic protein Bax, thereby specifically inhibiting the excessive apoptosis of cardiomyocytes in this subtype of injury. Its mechanism of action is clear and directly points to the apoptosis regulatory pathway, which is completely different from the mechanism of PCBP2 regulating ferroptosis in existing technologies.

Claims

1. The application of PCBP2 overexpression vector in the preparation of drugs for the treatment of myocardial ischemia-reperfusion injury, characterized in that, The myocardial ischemia-reperfusion injury described is an apoptosis-dominant type of myocardial ischemia-reperfusion injury, and the nucleotide sequence encoding PCBP2 is shown in SEQ ID NO.

1.

2. The application of the PCBP2 overexpression vector described in claim 1 to prepare a therapeutic drug for myocardial ischemia-reperfusion injury, characterized in that, The PCBP2 overexpression vector is an adeno-associated virus vector AAV9-PCBP2 that overexpresses the PCBP2 gene, containing a nucleotide sequence encoding PCBP2 and a myocardial-specific promoter; the myocardial-specific promoter is the cardiac troponin T promoter.

3. The application of the PCBP2 overexpression vector described in claim 2 to prepare a drug for treating myocardial ischemia-reperfusion injury, characterized in that, The medication for treating myocardial ischemia-reperfusion injury is an intravenous injection formulation.

4. The application of the PCBP2 overexpression vector described in claim 3 to prepare a drug for treating myocardial ischemia-reperfusion injury, characterized in that, The drug for treating myocardial ischemia-reperfusion injury has at least one of the following uses: (1) Restore the balance between pro-apoptotic protein Bax and anti-apoptotic protein Bcl2 after reperfusion and reduce cardiomyocyte apoptosis; (2) Reduce the area of ​​myocardial infarction after reperfusion; (3) Improve cardiac function after reperfusion.

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