Abstract:Objective: To investigate the effect and underlying mechanism of Danshen injection on endothelial angiogenesis in diabetic cardiomyopathy (DCM) rats via modulation of the vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Methods: A DCM rat model was established and the rats were randomly divided into model group, valsartan (40mg/kg, ig) group, and Danshen(Salvia miltiorrhiza) (2mL/kg, ip) group; with normal rats serving as the control group (n = 12 each group). After 4-week intervention, echocardiography and biochemical assays were used to measure left-ventricular ejection fraction (LVEF), left-ventricular fractional shortening (LVFS), mitral E/A ratio (Em/Am), fasting blood glucose (FBG), fasting insulin (FINS), creatine kinase-MB (CK-MB), and cardiac troponin I (cTnI). Myocardial histopathology and fibrosis were evaluated by HE and Masson staining; microvessel density (MVD) was determined by immunofluorescence; and myocardial protein expression of VEGF, VEGFR2, phosphorylated PI3K (p-PI3K), total PI3K, phosphorylated AKT (p-AKT), and total AKT was detected by Western blot. Results: Compared with the control group, the model group exhibited decreased LVEF, LVFS, and Em/Am, and increased FBG, FINS, CK-MB, and cTnI (P<0.05); disordered myocardial architecture, enlarged inter-fiber gaps, hypertrophied cardiomyocytes with inflammatory infiltration, and elevated collagen fraction (P<0.05); and reduced myocardial expression levels of VEGF, VEGFR2, p-PI3K/PI3K, and p-AKT/AKT (P<0.05). Relative to the model group, both valsartan and Danshen(Salvia miltiorrhiza) group exhibited increased levels of LVEF, LVFS, and Em/Am, and decreased levels of FBG, FINS, CK-MB, and cTnI (P<0.05); ameliorated myocardial structure, attenuated fiber rupture and collagen deposition, and lessened inflammatory infiltration (P<0.05); and up-regulated expression levels of VEGF, VEGFR2, p-PI3K/PI3K, and p-AKT/AKT(P<0.05). No significant differences in the above indices were observed between the valsartan and Danshen(Salvia miltiorrhiza) group (P>0.05). Conclusion: Danshen may attenuate myocardial injury in DCM rats by promoting endothelial angiogenesis via activation of the VEGF/VEGFR2 and PI3K/AKT signaling pathway.