Curcumin ameliorates myocardial fibrosis via TGF-β/Smads signaling pathway in diabetic rats / 中国药理学通报

ABSTRACT

Aim To investigate the role of TGF-β/Smads signaling pathway in the improvement of myo-cardial fibrosis in diabetes mellitus by curcumin. Methods A model of type 2 diabetes mellitus was in-duced by intraperitoneal injection of small dose of streptozotocin (STZ) 35 mg·kg-1with a high glucose and high fat diet, and then intervened by drinking of 300 mg·kg·d-1curcumin. The expression of myo-cardial collagen in rats was detected by Sirius red stai-ning. The expressions of Collange I and Collagen III in myocardium of rats were detected by immunofluores-cence. Cardiac fibroblasts(CFs) in neonatal rats were stimulated by different concentrations of glucose(5.5, 20,25, 30, 35, 50 mmol·L-1) for 24 h to deter-mine the optimum concentration of high glucose model, and rat CFs were stimulated for 24 h by 30 mmol·L-1 high glucose plus different concentrations of curcumin (10,25,50,100,200 μmol·L-1) to determine the optimal concentration of curcumin. The expressions of type Ⅰ and Ⅲ collagen,TGF-β1,p-Smad2,Smad2, p-Smad3,Smad3 and TβR-Ⅲin CFs were detected by Western blot. Results Compared with the control rats,the collagen deposition in the myocardium of the diabetic rats was more obvious and the expression of Collagen Ⅰ and Collagen Ⅲ significantly increased. After treatment of curcumin,the collagen deposition in the myocardium and the expression of Collagen I and CollagenⅢof diabetic rats remarkably decreased. The CFs under the condition of 30 mmol·L-1high glucose and 24 h had the highest survival rate (P <0.05);10μmol·L-1curcumin could obviously inhibit the proliferation of myocardial fibroblasts induced by high glucose (P<0.05). After induced by 30 mmol·L-1 high glucose for 24 h, the expression of Collagen Ⅰand Collagen Ⅲ, TGF-β1, p-Smad2, Smad2, p-Smad3,Smad3 and TβR-Ⅲ proteins in CFs markedly increased(P <0.05), and the expression levels of these proteins were obviously reduced when treated with 25 μmol·L-1curcumin. Conclusion Curcumin could ameliorate myocardial fibrosis in diabetic rats through TGF-β/Smads signaling pathway, exerting the protective effect on myocardium in diabetic rats.