麝香保心丸联合达格列净对心力衰竭大鼠肾脏纤维化的影响

Effect of Shexiang Baoxin Pills Combined with Dapagliflozin on Renal Fibrosis in Rats with Heart Failure

目的 探讨麝香保心丸和达格列净对心力衰竭大鼠肾脏纤维化的影响。方法 将Wistar雄性大鼠分为对照组(n=8)、模型组(n=9)、麝香保心丸组(n=8)、达格列净组(n=8)和麝香保心丸+达格列净组(n=8)。模型组及各药物组大鼠予以腹腔注射阿霉素制备心力衰竭模型,造模后各药物组分别给予相应药物灌胃。采用HE染色法观察大鼠肾脏组织病理学变化,Masson染色法观察肾脏纤维化情况并以胶原容积分数(CVF)评估胶原沉积情况;Western blotting法检测大鼠肾脏组织中转化生长因子-β1(TGF-β1)、Smad2、Smad3及Smad7蛋白表达情况。结果 模型组肾脏组织CVF高于对照组(P<0.01);各治疗组肾脏组织CVF低于模型组,且麝香保心丸+达格列净组低于麝香保心丸组、达格列净组(P<0.01)。与对照组比较,模型组较多炎性细胞浸润,肾脏纤维化显著,TGF-β1、Smad2、Smad3蛋白表达明显增加,Smad7蛋白表达下降(P<0.01);与模型组比较,麝香保心丸组、达格列净组及麝香保心丸+达格列净组肾脏纤维化程度减轻,TGF-β1和Smad3蛋白表达水平下降,Smad7蛋白表达水平升高(P<0.01)。结论 麝香保心丸和达格列净通过调控TGF-β1/Smads信号通路达到抗心力衰竭大鼠肾脏纤维化的作用,且两药联用效果优于单一用药。

Objective To investigate the effects of Shexiang Baoxin pills(SBP)and Dapagliflozin on renal fibrosis in rats with heart failure.Methods Wistar male rats were divided into control group(n=8),model group(n=9),Shexiang Baoxin pills group(n=8),Dagliazine group(n=8)and Shexiang Baoxin pills+Dagliazine group(n=8).The rats in the model group and the drug treatment groups were injected with Adriamycin intraperitoneally to establish the heart failure model,and then each drug treatment group was given the corresponding intragastric administration of drugs.Renal histopathology was observed by HE staining,renal fibrosis was observed by Masson staining,and collagen volume fraction(CVF)was used to evaluate the collagen deposition.The protein expressions of transforming growth faction-β1(TGF-β1),Smad2,Smad3 and Smad7 in renal tissues of rats were detected by Western blotting.Results CVF of renal tissue in model group was higher than that in control group(P<0.01).The CVF of renal tissue in all treatment groups was lower than that in model group,and lower in Shexiang Baoxin pills+Dagliazin group than in Shexiang Baoxin pill group and Dagliazin group(P<0.01).Compared with the control group,the model group had more inflammatory cell infiltration and renal fibrosis,significantly increased TGF-β1,Smad2,Smad3 protein expression,and decreased Smad7 protein expression(P<0.01).Compared with model group,the degree of renal fibrosis in Shexiang Baoxin pills group,Dagliazin group and Shexiang Baoxin pills+Dagliazin group was reduced,the protein expression levels of TGF-β1 and Smad3 were decreased,and the protein expression levels of Smad7 were increased(P<0.01).Conclusion Shexiang Baoxin pills and Dagliagazin can inhibit renal fibrosis in rats with heart failure by regulating TGF-β1/Smads signaling pathway,and the combined effect of the two drugs is better than that of single drug.