白芍总苷对糖尿病大鼠心肌纤维化的影响及机制研究

Effect of Total Glucosides of Paeony on Myocardial Fibrosis in Diabetic Rats and Underlying Mechanism

目的:研究白芍总苷(TGP)对糖尿病大鼠心肌纤维化的影响及其机制。方法:120只SD大鼠按随机数字表法分为6组:正常对照组、模型组、二甲双胍组(200 mg·kg^(-1))和TGP低、中、高剂量组(50,100,200 mg·kg^(-1)),每组20只。采用一次性腹腔注射链尿佐菌素(65 mg·kg^(-1))制备糖尿病大鼠模型;造模后连续8周灌胃给药,1次/d,正常对照组和模型组给予等量生理盐水。检测空腹血糖和血脂水平,脉冲多普勒检测心功能指标,Masson染色观察心肌纤维化程度并通过图像分析系统检测心肌间质胶原容积分数(CVF),Western blot法测定心肌胶原蛋白Ⅰ(Collagen Ⅰ)、Collagen Ⅲ、转化生长因子-β(TGF-β)、磷酸化Smad2(p-Smad2)蛋白表达水平。结果:与模型组比较,二甲双胍组和TGP中、高剂量组大鼠空腹血糖和总胆固醇(TC)、三酰甘油(TG)水平、左心室舒张末期内径(LVIDd)、左心室收缩末期左室内径(LVIDs)显著降低,射血分数(EF)、每搏输出量(SV)显著升高(P<0.05);纤维化程度明显减轻、CVF显著降低,心肌组织Collagen Ⅰ、Collagen Ⅲ、TGF-β、p-Smad2蛋白表达显著下调(P<0.05)。TGP高剂量组与二甲双胍组比较,除空腹血糖和LVIDd外,其余各指标差异均有统计学意义(P<0.05)。结论:TGP对糖尿病大鼠心肌纤维化具有抑制作用,机制可能与抑制TGF-β/Smad信号通路、下调Collagen Ⅰ和Collagen Ⅲ表达有关。

Objective: To investigate the effect of total glucosides of paeony( TGP) on myocardial fibrosis in diabetic rats and its mechanism. Methods: Totally 120 SD rats were randomly divided into 6 groups: normal control group,model group,metformin group( 200 mg·kg^(-1)) and TGP low,medium and high dose groups( 50,100 and 200 mg·kg^(-1)) with 20 ones per group. The diabetic rat model was established by intraperitoneal injection of streptozotocin( 65 mg·kg^(-1)). After the model was established successfully,the drugs were given by gavage simultaneously,once a day for 8 weeks,while the normal control group and the model group were given equal amount of saline. The level of fasting blood glucose and blood lipid levels were detected,cardiac function indices were detected by pulse doppler,myocardial fibrosis degree were observed by Masson staining,CVF was detected by image analysis system,and the expressions of Collagen Ⅰ,Collagen Ⅲ,TGF-β and p-Smad2 protein in myocardial tissue were detected by Western blot method. Results: Compared with those in the model group,the fasting blood glucose,levels of TC and TG,LVIDd and LVIDs of rats in metformin group and TGP medium and high dose groups were significantly decreased,and EF and SV were significantly increased( P<0.05). The fibrosis degree of myocardium and CVF were significantly decreased,and the expressions of Collagen Ⅰ,Collagen Ⅲ,TGF-β and pSmad2 were significantly decreased( P<0.05). Compared with TGP high dose group and metformin group,except fasting blood glucose and LVIDd,the differences in the other indicators were statistically significant( P< 0.05). Conclusion: TGP has inhibitory effect on myocardial fibrosis in diabetic rats,and its mechanism may be related to the inhibition of TGF-β/Smad signal pathway and down-regulation of Collagen Ⅰ and Collagen Ⅲ.