AIM  To investigate the protective effect and mechanism of Shuangshen Granule (SG) on cardiac functions in rats with myocardial infarction.

  METHODS  Sixty male SPF SD rats were randomly divided into six groups: myocardial infarction model group (MI group, n=10), sham operation group (sham group, n=10), SG low-dose group (SG-L group, n=10), SG medium-dose group (SG-M group, n=10), SG high-dose group (SG-H group, n=10) and compound salvia miltiorrhise dropping pill group (CDDP group, n=10). Hemodynamic analysis and echocardiogram examination were performed, the content of serum-related indicators was determined, rat myocardial tissue was separated, capillary density was detected and expression levels of adhesion molecule-1 (PECAM-1/CD31) of platelet endothelial cells in myocardial tissue were also detected. Western blot was used to detect the expression levels of myocardial TGF-β1 and Smad2/3 proteins as well as phosphoryl inositin 3-kinase (p-P13K) and phosphorylated protein kinase B (p-A) protein expression levels of rapamycin target protein (p-mTOR) in TK and phosphorylated mammals.

  RESULTS  Compared with Sham group, the hemodynamic indexes of MI group were significantly different (P<0.05), and could be partially recovered by SG treatment. Compared with that in MI group, the LDL-C content decreased only in SG-H and CDDP groups (P<0.05). The levels of CK and CK-MB in SG-L, SG-M, SG-H and CDDP groups decreased significantly compared with that in MI group (P<0.05) and they were dose-dependent. Compared with those in SG-L, SG-M, SG-H and CDDP groups, the myocardial infarction area was the largest in MI group, the ventricular wall was thinner, myocardial cell count was less and collagen fiber structure was disordered in the infarction area. Compared with that in MI group (34.29%±3.86%), SG-M and SG-H doses reduced the area of myocardial infarction respectively to (15.07%±1.50%) and (14.58%±1.46%). Compared with that in MI group, the capillary densities in SG-L, SG-M, SG-H and CDDP groups increased significantly (P<0.05). The expression levels of p-P13K, p-ATK and p-mTOR protein in SG-L, SG-M, SG-H and CDDP groups were significantly higher than that in MI group (P<0.05). Immune staining tests showed that CD31-positive expression levels in each SG group and CDDP group were significantly higher than that in MI group, showing a dose-dependent relationship (P<0.05). Compared with those in sham group, the expression levels of TGF-β1 and Smad2/3 proteins in MI group were enhanced, whereas the expression levels of Smad2/3 protein in SG-L, SG-M, SG-H and CDDP groups and the expression level of TGF-β1 in SG-H group were significantly reduced.

  CONCLUSION  Shuangshen Granules can promote angiogenesis and protect myocardium, which can activate PI3k-Akt-mTOR signal, increase VEGF level and inhibit autophagy.