The study of salvianolic acid B on the improvement of myocardial fibrosis in diabetic rats by RhoA/ROCKl pathway / 中国药理学通报

ABSTRACT

Objective To investigate the effect and mechanism of salvianolic acid B(SalB)on myocardial fibrosis in diabetic rats based on RhoA/ROCK1 signaling pathway.Methods Diabetic rat model was established by injecting streptozotocin into tail vein of healthy male SD rats.At the end of the 12th week, the collagen fiber expression in the left ventricular myocardium of rats was detected by Sirius Red reagent staining.The protein expressions of α-SMA, Collagen and Collagen III in left ventricular myocardium were detected by Western blot.Cardiac fibroblasts(CFs)were cultured in SD rats by differential adhesion, and CFs were pretreated with different concentrations of SalB(12.5, 25, 50 μmol·L-1)for 1 h, and the optimal dose was determined by high glucose induction.RhoA protein expression in CFs was detected by immunofluorescence; the protein expressions of α-SMA, Collagen , Collagen III, RhoA and ROCK1 in CFs were detected by Western blot.Results Compared with the normal control group, the expression of collagen in left ventricular myocardium of diabetic rats increased significantly, and the expression of α-SMA, Collagen and Collagen III increased significantly.After SalB intervention, the expression of collagen decreased significantly, and the expression of the above proteins decreased significantly(P<0.01).The expression of α-SMA, Collagen , Collagen III, RhoA and ROCK1 in CFs stimulated with 25 mmol·L-1 high glucose for 24 h was significantly increased.After pretreatment with SalB(25 μmol·L-1)and inhibitor Y-27632(10 μmol·L-1), the activity of CFs was significantly inhibited, and the expression of these proteins was significantly decreased(P<0.01).Conclusion SalB can improve myocardial fibrosis in diabetic rats, and has a certain role in protecting the myocardium of diabetic rats.The mechanism may be related to the inhibition of RhoA/ROCK1 signaling pathway.