Application of SDHAF4-targeting reagent and / or medicament in preparation of medicine for treating cardiac hypertrophy

Abstract

The invention belongs to the technical field of biological medicine, and particularly relates to application of a reagent and / or medicament of targeted SDHAF4 in preparation of a medicine for treating myocardial hypertrophy. According to the application disclosed by the invention, the protective effect of the ginsenoside Rg3 on cardiac hypertrophy is defined through experiments, a Keap1 / Nrf2 pathway is proved to be a key mechanism for down-regulating mtROS by the ginsenoside Rg3, and SDHAF4 is revealed to be an action target of the ginsenoside Rg3 at the same time. An innovative path is opened up for prevention and treatment of cardiac hypertrophy, a new drug intervention target is established, and the breakthrough discovery not only broadens the boundary of cardiovascular disease treatment strategies, but also adds key power for promoting the internationalization process of traditional Chinese medicine.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and particularly relates to the application of a reagent and / or medicament targeting SDHAF4 in the preparation of a medicament for treating myocardial hypertrophy. Background Art

[0002] Among many risk factors for cardiovascular diseases, myocardial hypertrophy is particularly special. Its main pathological features are myocardial wall thickening, narrow heart cavity, increased myocardial oxygen demand, and myocardial cell function damage. However, there is currently no effective clinical treatment. Previous studies have shown that the accumulation of mitochondrial reactive oxygen species (mtROS) is a key factor promoting myocardial cell hypertrophy and cardiac hypertrophy, but its molecular mechanism is still unclear. Traditional Chinese medicine ginseng has extensive pharmacological activities in the prevention and treatment of cardiovascular diseases. Ginsenoside Rg3 is the main active ingredient in ginseng. Whether it can participate in the mechanism of myocardial hypertrophy progression by regulating mtROS generation has not been reported. Therefore, further clarifying the regulatory mechanism of ginsenoside Rg3 in mtROS generation will provide new molecular intervention targets and clinical treatment strategies for the prevention and treatment of myocardial hypertrophy. Summary of the Invention

[0003] The purpose of the present invention is to provide the application of a reagent and / or medicament targeting SDHAF4 in the preparation of a medicament for treating myocardial hypertrophy. The present invention has clearly demonstrated the protective effect of ginsenoside Rg3 on myocardial hypertrophy through experiments, revealed that SDHAF4 is the action target of ginsenoside Rg3, opened up an innovative path for the prevention and treatment of myocardial hypertrophy, and established a new drug intervention target.

[0004] The present invention provides the application of a reagent and / or medicament targeting SDHAF4 in the preparation of a medicament for treating myocardial hypertrophy.

[0005] As a preferred embodiment, the active ingredient of the reagent and / or medicament targeting SDHAF4 comprises ginsenoside Rg3.

[0006] As a preferred embodiment, the ginsenoside Rg3 includes 20(S) stereoisomer and 20(R) stereoisomer.

[0007] As a preferred embodiment, based on the body weight of the mouse, the dosage of the ginsenoside Rg3 is 3 - 7 mg / kg / d.

[0008] The present invention also provides a medicament targeting SDHAF4, and the medicament targeting SDHAF4 comprises ginsenoside Rg3 and a pharmaceutically acceptable excipient or carrier.

[0009] As a preferred embodiment, the preparation forms of the drug targeting SDHAF4 include tablets, pills, powders or injections.

[0010] As a preferred embodiment, the administration method of the drug targeting SDHAF4 includes injection.

[0011] The present invention also provides a method for screening drugs for treating myocardial hypertrophy, including the following steps: mixing a candidate drug with a myocardial hypertrophy cell model or a myocardial hypertrophy animal model, and detecting the expression of SDHAF4.

[0012] As a preferred embodiment, when the protein expression level of SDHAF4 decreases or the expression level of the SDHAF4 gene decreases, it indicates that the candidate drug can be used to treat myocardial hypertrophy.

[0013] As a preferred embodiment, the detection includes detecting the protein expression level of SDHAF4 by Western blot or detecting the expression level of the SDHAF4 gene by fluorescence quantitative PCR.

[0014] Beneficial effects: The present invention provides the application of a reagent and / or medicament targeting SDHAF4 in the preparation of a drug for treating myocardial hypertrophy. Through experiments, the present invention clarifies the protective effect of ginsenoside Rg3 on myocardial hypertrophy, confirms that the Keap1 / Nrf2 pathway is the key mechanism for ginsenoside Rg3 to down-regulate mtROS, and reveals that SDHAF4 is the action target of ginsenoside Rg3. The present invention opens up an innovative path for the prevention and treatment of myocardial hypertrophy and establishes a new drug intervention target. This breakthrough discovery not only broadens the boundaries of cardiovascular disease treatment strategies, but also adds a key driving force to the internationalization process of traditional Chinese medicine. Description of the Drawings

[0015] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required in the embodiments.

[0016] Figure 1 For ginsenoside Rg3 in Example 1, it inhibits the level of the myocardial cell hypertrophy marker protein ANP in a time- and dose-dependent manner; wherein A shows the change in ANP protein expression after treating H9C2 myocardial cells with angiotensin II and different concentrations of ginsenoside Rg3; B shows the change in ANP protein expression after treating H9C2 myocardial cells with angiotensin II and ginsenoside Rg3 (10 -3 μM) for different times; *P<0.05, vs Control, n = 3;

[0017] Figure 2After treating the SD rat hypertrophy model with ginsenoside Rg3 and angiotensin II in Example 1, the fluorescence intensity was significantly reduced;

[0018] Figure 3 After treating the SD rat hypertrophy model with ginsenoside Rg3 and angiotensin II in Example 1, the fluorescence intensity of mtROS was significantly reduced;

[0019] Figure 4 After treating H9C2 cardiomyocytes with angiotensin II and different concentrations of ginsenoside Rg3 in Example 2, the expression change of Keap1 protein; *P<0.05, vs Control, n = 3;

[0020] Figure 5 After treating H9C2 cardiomyocytes with angiotensin II and ginsenoside Rg3 at different times (10 -3 μM) in Example 2, the expression change of Keap1 protein; *P<0.05, vs Control, n = 3;

[0021] Figure 6 Co-localization of Nrf2 and the proteasome probe in Example 2;

[0022] Figure 7 After treating H9C2 cardiomyocytes with ginsenoside Rg3 and the Keap1 / Nrf2 pathway inhibitor ML-385 in Example 2, the change of mtROS fluorescence;

[0023] Figure 8 Predicted molecular docking map of ginsenoside Rg3 and SDHAF4 in Example 3; where A is the basic model of molecular docking; B is the ball-and-stick model of molecular docking;

[0024] Figure 9 After treating H9C2 cardiomyocytes with angiotensin II and different concentrations and different times of ginsenoside Rg3 in Example 3, the expression change of SDHAF4 protein; where A is the expression change of SDHAF4 protein after treating H9C2 cardiomyocytes with angiotensin II and different concentrations of ginsenoside Rg3; B is the expression change of SDHAF4 protein after treating H9C2 cardiomyocytes with angiotensin II and ginsenoside Rg3 at different times (10 -3 μM); *P<0.05, vs Control, n = 3;

[0025] Figure 10 Schematic diagram of the scientific hypothesis. Detailed implementation manners

[0026] The present invention provides the use of a reagent and / or medicament targeting SDHAF4 (succinate dehydrogenase complex assembly factor 4) in the preparation of a medicament for treating myocardial hypertrophy. As a specific embodiment, the active ingredient of the reagent and / or medicament targeting SDHAF4 comprises ginsenoside Rg3. The ginsenoside Rg3 includes 20(S) stereoisomer and 20(R) stereoisomer. As a specific embodiment, the SDHAF4 is one of the main members of the succinate dehydrogenase family, located in the mitochondrial matrix, and plays an important role in the tricarboxylic acid (TCA) cycle and the regulation of mitochondrial homeostasis.

[0027] As a specific embodiment, the molecular docking software AutodockVina 1.2.2 was used to evaluate the binding energy and interaction correlation between ginsenoside Rg3 and SDHAF4. It was found that there was a low binding energy of -15.262 kcal / mol between ginsenoside Rg3 and SDHAF4, indicating that the binding between ginsenoside Rg3 and SDHAF4 was highly stable; Western blot detection showed that ginsenoside Rg3 down-regulated the expression level of SDHAF4 in a time- and dose-dependent manner, indicating that SDHAF4 was an important target of the action of ginsenoside Rg3.

[0028] In the present invention, based on the body weight of mice, the dosage of ginsenoside Rg3 is 3-7 mg / kg / d. As a specific embodiment, based on the body weight of mice, the dosage of ginsenoside Rg3 can be any one of 3 mg / kg / d, 4 mg / kg / d, 5 mg / kg / d, 6 mg / kg / d, and 7 mg / kg / d.

[0029] The present invention also provides a medicament targeting SDHAF4. The medicament targeting SDHAF4 comprises ginsenoside Rg3 and a pharmaceutically acceptable excipient or carrier. The preparation form of the medicament targeting SDHAF4 includes tablets, pills, powders or injections, and the usage mode of the medicament targeting SDHAF4 includes injection.

[0030] As a specific embodiment, the medicament targeting SDHAF4 can inhibit the activity of the Keap1 / Nrf2 pathway. The examples of the present invention show that ginsenoside Rg3 down-regulates the level of Keap1 protein and promotes the co-localization of Nrf2 and the proteasome probe; ginsenoside Rg3 down-regulates the increase in mtROS level mediated by the Keap1 / Nrf2 pathway inhibitor ML-385. It indicates that the Keap1 / Nrf2 pathway is an important pathway for ginsenoside Rg3 to down-regulate the mtROS level.

[0031] The present invention also provides a method for screening drugs for treating myocardial hypertrophy, comprising the following steps: mixing a candidate drug with a myocardial hypertrophy cell model or a myocardial hypertrophy animal model, and detecting the expression of SDHAF4. As a specific embodiment, the detection includes detecting the protein expression level of SDHAF4 by Western blot or detecting the expression level of the SDHAF4 gene by fluorescence quantitative PCR. As a specific embodiment, when the candidate drug is mixed with the myocardial hypertrophy cell model or the myocardial hypertrophy animal model, if the protein expression level of SDHAF4 decreases or the expression level of the SDHAF4 gene decreases, it is preliminarily proved that the candidate drug can be used for treating myocardial hypertrophy; when the candidate drug is mixed with the myocardial hypertrophy cell model or the myocardial hypertrophy animal model, if the protein expression level of SDHAF4 does not decrease or the expression level of the SDHAF4 gene does not decrease, it is preliminarily proved that the candidate drug cannot be used for treating myocardial hypertrophy.

[0032] The technical solution of the present invention proves that ginsenoside Rg3 down-regulates the expression of SDHAF4, inhibits the activity of the Keap1 / Nrf2 pathway, reduces the level of mtROS, and delays the occurrence and development of myocardial hypertrophy.

[0033] The present invention has clearly defined the protective effect of ginsenoside Rg3 on myocardial hypertrophy through experiments, confirmed that the Keap1 / Nrf2 pathway is the key mechanism for ginsenoside Rg3 to down-regulate mtROS, and revealed that SDHAF4 is the action target of ginsenoside Rg3. The present invention opens up an innovative path for the prevention and treatment of myocardial hypertrophy and establishes a new drug intervention target. This breakthrough discovery not only broadens the boundaries of cardiovascular disease treatment strategies but also adds a key driving force to promoting the internationalization process of traditional Chinese medicine.

[0034] To further illustrate the present invention, the following examples will be used to describe in detail the application of the reagent and / or medicament targeting SDHAF4 in the preparation of drugs for treating myocardial hypertrophy, but they should not be construed as limiting the protection scope of the present invention.

[0035] Unless otherwise specified, the present invention has no special requirements for the preparation raw materials, and commercially available products well-known to those skilled in the art can be used.

[0036] Example 1 Observation of the effect of ginsenoside Rg3 on the occurrence and development of myocardial hypertrophy

[0037] H9C2 cardiomyocytes (manufacturer: Fuheng Biology, product number: FH1004) and SD rats were treated with angiotensin II to establish a myocardial hypertrophy model (angiotensin II induction is one of the commonly used drugs for H9C2 cardiomyocyte hypertrophy; the SD rat hypertrophy model requires not only angiotensin II induction but also TAC surgery).

[0038] A: Treat H9C2 cardiomyocytes with angiotensin II and ginsenoside Rg3 (brand: MCE, catalog number: 14197-60-5) at different concentrations. The first group was treated with 10 -3 μM angiotensin II and 0 μM ginsenoside Rg3 to treat H9C2 cardiomyocytes; the second group was treated with 10 -3 μM angiotensin II and 10 -6 μM ginsenoside Rg3 to treat H9C2 cardiomyocytes; the third group was treated with 10 -3 μM angiotensin II and 10 -5 μM ginsenoside Rg3 to treat H9C2 cardiomyocytes; the fourth group was treated with 10 -3 μM angiotensin II and 10 -4 μM ginsenoside Rg3 to treat H9C2 cardiomyocytes; the fifth group was treated with 10 -3 μM angiotensin II and 10 -3 μM ginsenoside Rg3 to treat H9C2 cardiomyocytes. After 24 h of treatment, samples were taken for Western blot to detect the expression of ANP protein, and the gray value of the ANP band was analyzed using software such as ImageJ, with 3 replicates for each treatment ( Figure 1 in A).

[0039] Treat H9C2 cardiomyocytes with 10 -3 μM angiotensin II and 10 -3 μM ginsenoside Rg3. Samples were taken at 0 h, 6 h, 12 h, 18 h, and 24 h after treatment respectively for Western blot to detect the expression of ANP protein, and the gray value of the ANP band was analyzed using software such as ImageJ, with 3 replicates for each time point ( Figure 1 in B).

[0040] Western blot. The specific method is as follows: 1. Sample preparation, lysing cells / tissues: Use RIPA lysis buffer (containing protease and phosphatase inhibitors) to lyse the samples, incubate on ice for 30 min, centrifuge (12,000×g, 15 min, 4°C), and take the supernatant. Determine the protein concentration: Measure by BCA or Bradford method, adjust to the same concentration, and perform denaturation treatment: Add SDS-PAGE loading buffer, boil at 95°C for 10 min to denature the protein. 2. SDS-PAGE gel preparation, select the separating gel concentration according to the molecular weight of the target protein (e.g., 10% for 30 - 200 kDa), and the upper layer is the stacking gel (5%); Loading: Load 20 μg of protein per well, add prestained protein Marker; Electrophoresis conditions: 80 V for the stacking gel, 120 V for the separating gel, stop when the bromophenol blue reaches the bottom of the gel. 3. Transfer membrane, activate the membrane: PVDF membrane needs to be soaked in methanol for 1 min, while nitrocellulose membrane does not; Transfer membrane assembly: Assemble in the order of "cathode - sponge - filter paper - gel - membrane - filter paper - sponge - anode", ensuring no bubbles; Transfer membrane conditions: Constant voltage of 100 V, transfer for 2 h in an ice bath. 4. Blocking, dissolve 5% skim milk or BSA (BSA is recommended for phosphorylated proteins) in TBST, block at room temperature for 1 h or overnight at 4°C. 5. Antibody incubation, primary antibody incubation: Dilute the primary antibody with the blocking solution (according to the ratio in the instruction manual, e.g., 1:1000), incubate overnight at 4°C or for 2 h at room temperature, wash 3 times with TBST for 10 min each; Secondary antibody incubation: HRP-labeled secondary antibody (e.g., 1:5000), incubate at room temperature for 1 h, wash 3 times with TBST for 10 min each. 6. ECL development: Mix equal volumes of ECLA / B solution, drop it on the membrane, and react in the dark for 1 min. Detect the protein expression level of ANP.

[0041] Results: Figure 1 In Figure A, after treating H9C2 cardiomyocytes with angiotensin II and different concentrations of ginsenoside Rg3, the changes in ANP protein expression were shown. It can be seen from the results that as the concentration of ginsenoside Rg3 increased, the expression level of ANP, a marker protein of cardiomyocyte hypertrophy, gradually decreased. Figure 1 In Figure B, after treating H9C2 cardiomyocytes with angiotensin II and ginsenoside Rg3 (10 -3 μM) for different times, the changes in ANP protein expression were shown. It can be seen from the results that as the treatment time of ginsenoside Rg3 increased, the expression level of ANP protein gradually decreased. It indicates that ginsenoside Rg3 inhibits the level of ANP, a marker protein of cardiomyocyte hypertrophy, in a time- and dose-dependent manner.

[0042] B: Select 90 SD rats with body weight controlled at 200 ± 10 g, and randomly divide them into three groups.

[0043] The first group was subcutaneously injected with DMSO in the back as a control, the second group was injected with ginsenoside Rg3 (brand: MCE, catalog number: 14197-60-5, 5 mg / kg / d), and the third group was injected with angiotensin II (5 mg / kg / d) after injecting ginsenoside Rg3. All rats had free access to food and water for 14 days.

[0044] The heart tissues of SD rats in the first, second, and third groups were taken for fluorescence intensity observation (see Figure 2 ). The heart tissues of SD rats in the first, second, and third groups were taken, and the mtROS levels of the three groups of samples were detected using a mitochondrial reactive oxygen species kit (manufacturer: Beyotime; catalog number: S0061S) ( Figure 3 ), and the specific operation is shown in the instruction manual.

[0045] Results: Figure 2 After treating the SD rat hypertrophy model with ginsenoside Rg3 and angiotensin II, the fluorescence intensity was significantly reduced. Figure 3 After treating the SD rat hypertrophy model with ginsenoside Rg3 and angiotensin II, the mtROS fluorescence intensity was significantly reduced, indicating that ginsenoside Rg3 can inhibit the level of mitochondrial mtROS, thereby alleviating myocardial hypertrophy.

[0046] Example 2 confirmed that the Keap1 / Nrf2 pathway is the key mechanism for ginsenoside Rg3 to down-regulate mtROS

[0047] H9C2 cardiomyocytes were treated with angiotensin II and different concentrations of ginsenoside Rg3. The first group was treated with 10 -3 μM of angiotensin II and 0 μM of ginsenoside Rg3; the second group was treated with 10 -3 μM of angiotensin II and 10 -5 μM of ginsenoside Rg3; the third group was treated with 10 -3 μM of angiotensin II and 10 -4 μM of ginsenoside Rg3; the fourth group was treated with 10 -3 μM of angiotensin II and 10 -3 μM of ginsenoside Rg3. After 24 hours of treatment, samples were taken for Western blot to detect the expression of Keap1 protein, and the gray value of the bands was statistically analyzed. Each treatment had 3 replicates (the Western blot detection method and the statistical method of the expression gray level were the same as those in Example 1).

[0048] Using angiotensin II (10 -3 μM) and ginsenoside Rg3 (10 -3H9C2 cardiomyocytes were treated with angiotensin II and different concentrations of ginsenoside Rg3 (10 μM). Samples were taken at 0 h, 6 h, 12 h, and 24 h after treatment, and the expression level of Keap1 protein was detected by Western blot. The gray value of the band was statistically analyzed, and there were 3 replicates at each time point (the Western blot detection method and the statistical method of the expression gray level were the same as those in Example 1).

[0049] To confirm that the Keap1 / Nrf2 pathway is the key mechanism by which ginsenoside Rg3 downregulates mtROS, after treating with the Keap1 / Nrf2 pathway inhibitor ML-385 (manufacturer: MCE; catalog number: HY-100523) and ginsenoside Rg3 for 24 h, the cell diameter was observed and statistically analyzed by a 2.5D microscope; the cell volume change was observed by scanning electron microscopy; the change level of mtROS was detected by a mitochondrial reactive oxygen species kit (manufacturer: Beyotime; catalog number: S0061S).

[0050] Results: Figure 4 For the change in the expression of Keap1 protein after treating H9C2 cardiomyocytes with angiotensin II and different concentrations of ginsenoside Rg3, it can be seen from the results that as the concentration of ginsenoside Rg3 increases, the expression level of Keap1 protein gradually decreases. Figure 5 For the change in the expression of Keap1 protein after treating H9C2 cardiomyocytes with angiotensin II and ginsenoside Rg3 (10 μM) for different times, it can be seen from the results that as the treatment time of ginsenoside Rg3 increases, the expression level of Keap1 protein gradually decreases. It is shown that ginsenoside Rg3 downregulates the level of Keap1 in a time- and dose-dependent manner. -3 For the change in the expression of Keap1 protein after treating H9C2 cardiomyocytes with angiotensin II and ginsenoside Rg3 (10 μM) for different times, it can be seen from the results that as the treatment time of ginsenoside Rg3 increases, the expression level of Keap1 protein gradually decreases. It is shown that ginsenoside Rg3 downregulates the level of Keap1 in a time- and dose-dependent manner.

[0051] Figure 6 It is the co-localization of Nrf2 and the proteasome probe. Figure 7 For the fluorescence change of mtROS after treating H9C2 cardiomyocytes with ginsenoside Rg3 and the Keap1 / Nrf2 pathway inhibitor ML-385, it can be seen from the results that treating H9C2 cardiomyocytes with the Keap1 / Nrf2 pathway inhibitor ML-385 alone can enhance the fluorescence level of mitochondrial mtROS, and treating with ginsenoside Rg3 and ML-385 together can inhibit the fluorescence level of mtROS induced by ML-385, indicating that ginsenoside Rg3 downregulates the increase in mtROS level mediated by the Keap1 / Nrf2 pathway inhibitor ML-385, and the Keap1 / Nrf2 pathway is an important pathway for ginsenoside Rg3 to downregulate the mtROS level.

[0052] Example 3 clarifies that SDHAF4 regulates Keap1 / Nrf2 as an important target for mtROS-mediated myocardial hypertrophy

[0053] H9C2 cardiomyocytes and SD rats were treated with angiotensin II to establish a myocardial hypertrophy model. To prove that SDHAF4 regulates Keap1 / Nrf2 and is an important target for mtROS-mediated myocardial hypertrophy, protein-molecule docking prediction of SDHAF4 and ginsenoside Rg3 was performed using AutodockVina 1.2.2 software.

[0054] H9C2 cardiomyocytes were treated with angiotensin II and different concentrations of ginsenoside Rg3. The first group was treated with 10 -3 μM angiotensin II and 0 μM ginsenoside Rg3; the second group was treated with 10 -3 μM angiotensin II and 10 -6 μM ginsenoside Rg3; the third group was treated with 10 -3 μM angiotensin II and 10 -5 μM ginsenoside Rg3; the fourth group was treated with 10 -3 μM angiotensin II and 10 -4 μM ginsenoside Rg3; the fifth group was treated with 10 -3 μM angiotensin II and 10 -3 μM ginsenoside Rg3. After 24 h of treatment, samples were taken for Western blot to detect the protein expression of SDHAF4, and the gray value of the band was statistically analyzed. Each treatment had 3 replicates (the Western blot detection method and the statistical method of the expression gray level were the same as those in Example 1).

[0055] H9C2 cardiomyocytes were treated with 10 -3 μM angiotensin II and 10 -3 μM ginsenoside Rg3. Samples were taken at 0 h, 6 h, 12 h, 18 h, and 24 h after treatment for Western blot to detect the protein expression of SDHAF4, and the gray value of the band was statistically analyzed. Each time point had 3 replicates (the Western blot detection method and the statistical method of the expression gray level were the same as those in Example 1).

[0056] Results: The molecular docking prediction of ginsenoside Rg3 and SDHAF4 is shown in Figure 8 , indicating that ginsenoside Rg3 can interact with SDHAF4, and there is a low binding energy of -15.262 kcal / mol between the two, indicating that the binding between the two is highly stable. Figure 9It is shown that ginsenoside Rg3 downregulates the expression level of SDHAF4 in a time- and dose-dependent manner, and SDHAF4 is the target of ginsenoside Rg3. Therefore, SDHAF4 mediates the regulation of the Keap1 / Nrf2 pathway by ginsenoside Rg3, downregulates the level of mtROS, and alleviates myocardial hypertrophy.

[0057] Based on the comprehensive experimental results, the following scientific hypothesis is proposed: "Ginsenoside Rg3 downregulates the expression of SDHAF4, inhibits the activity of the Keap1 / Nrf2 pathway, reduces the level of mtROS, and delays the occurrence and development of myocardial hypertrophy", as shown in Figure 10 .

[0058] Thus, through experiments, the present invention has clarified the protective effect of ginsenoside Rg3 on myocardial hypertrophy, confirmed that the Keap1 / Nrf2 pathway is the key mechanism for ginsenoside Rg3 to downregulate mtROS, and at the same time revealed that SDHAF4 is the target of ginsenoside Rg3. The present invention has opened up an innovative path for the prevention and treatment of myocardial hypertrophy and established a new drug intervention target. This breakthrough discovery not only broadens the boundaries of cardiovascular disease treatment strategies but also adds a key driving force to the promotion of the internationalization process of traditional Chinese medicine.

[0059] Although the above embodiments have described the present invention in detail, they are only a part of the embodiments of the present invention, not all of them. People can also obtain other embodiments based on these embodiments without creative efforts, and these embodiments all fall within the protection scope of the present invention.

Claims

1. Use of a reagent and / or medicament targeting SDHAF4 in the preparation of a drug for treating myocardial hypertrophy.

2. The application according to claim 1, wherein The active ingredient of the reagent and / or medicament targeting SDHAF4 contains ginsenoside Rg3.

3. The application according to claim 2, wherein The ginsenoside Rg3 includes 20(S) stereoisomer and 20(R) stereoisomer.

4. The application according to claim 2, characterized in that Based on the body weight of the mouse, the dosage of the ginsenoside Rg3 is 3 - 7 mg / kg / d.

5. A drug targeting SDHAF4, characterized in that, The drug targeting SDHAF4 contains ginsenoside Rg3 and excipients or carriers permitted by the drug.

6. The drug according to claim 5, characterized in that, The preparation form of the drug targeting SDHAF4 includes tablets, pills, powders or injections.

7. The medicament according to claim 5 or 6, characterized in that, The usage mode of the drug targeting SDHAF4 includes injection.

8. A method for screening drugs for treating myocardial hypertrophy, characterized in that, It includes the following steps: mixing a candidate drug with a myocardial hypertrophy cell model or a myocardial hypertrophy animal model, and detecting the expression of SDHAF4.

9. The method according to claim 8, wherein When a decrease in the protein expression level of SDHAF4 or a decrease in the expression level of the SDHAF4 gene is detected, it indicates that the candidate drug can be used to treat myocardial hypertrophy.

10. The method according to claim 8 or 9, characterized in that, The detection includes detecting the protein expression level of SDHAF4 by Western blot or detecting the expression level of the SDHAF4 gene by fluorescence quantitative PCR.

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