科研之友
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摘要
OBJECTIVE To investigate the effects of Astragaloside Ⅳ(which can be extracted from the traditional Chinese medicine Astragalus membranaceus) on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS Model of heart failure(HF) after AMI was established with ligation of left anterior descending artery on Sprague-Dawley(SD) rats. The rats were divided into three groups: sham, model and Astragaloside IV treatment group.Twenty-eight days after treatment(Astragaloside Ⅳ, 20 mg·kg-1 daily), hematoxylin-eosin(HE) staining was applied to visualize cardiomyocyte morphological changes. High performance liquid chromatography(HPLC) was performed to assess the contents of adenosine phosphates in heart. Positron emission tomography and computed tomography(PET-CT)was conducted to evaluate the cardiac glucose metabolism. Expressions of key molecules such as peroxisome proliferator-activated receptor γ(PPARγ), sterol carrier protein 2(SCP2) and long chain acyl Co A dehydrogenase(ACADL) were measured by western blotting(WB) and immunohistochemistry(IHC). Oxygen-glucose deprivation-reperfusion(OGD/R)-induced H9 C2 injury cardiomyocyte model was adopted for potential mechanism research in vitro. RESULTS Treatment with Astragaloside Ⅳ rescued hearts from structural and functional damages as well as inflammatory infiltration.Levels of adenosine triphosphate(ATP) and energy charge(EC) in Astragaloside Ⅳ group were also up-regulated compared to model group. Further results demonstrated that critical enzymes both in lipid metabolism and glucose metabolism compromised in model group compared to sham group. Intriguingly, Astragaloside Ⅳ could up-regulate critical enzymes including ACADL and SCP2 in lipid metabolism accompanying with promoting effect on molecules in glycolysis simulta-neously. Results on upstreaming signaling pathway demonstrated that Astragaloside Ⅳ could dramatically increase the expressions of PPARγ. In vitro study suggested the efficacy of Astragaloside Ⅳ could be blocked by T0070907, a selective PPARγ inhibitor. CONCLUSION Astragaloside IV has cardioprotective effect in improving cardiac function and energy metabolism through regulating lipid and glucose metabolism. The effects may be mediated by PPARγ pathway.
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