基于TGF-β1/Smads信号通路探讨抗纤益心方对心肌纤维化时相性对扩张型心肌病模型大鼠的影响

Effects of Kangxian Yixin Recipe on Phase of Myocardial Fibrosis on Dilated Cardiomyopathy Model Rats Based on TGF-β1/Smads Signaling Pathway

目的:基于转化生长因子-β1(transforming growth factor-β1,TGF-β1)/Smads信号通路探讨抗纤益心方对扩张型心肌病(dilated cardiomyopathy,DCM)模型大鼠的影响。方法:运用呋喃唑酮水溶液制备DCM大鼠模型,将制备成功的模型大鼠随机分为模型对照组、小剂量抗纤益心方组(4.7 g·kg^(-1))、大剂量抗纤益心方组(18.8 g·kg^(-1))、贝那普利组(10.125 mg·kg^(-1))、联合用药组(抗纤益心方18.8 g·kg^(-1))及造模不同时间点组、空白对照组。所有组全程给予呋喃唑酮饮水喂养,给药组于造模第6周开始给予相应的药物,连续给药8周,造模组分别于对应时间点检测相关指标。分别检测大鼠超声心动图,免疫组织法检测心肌组织Ⅰ型胶原、Ⅲ型胶原、TGF-β1的表达,RT-PCR及Western Blot法检测心肌TGF-β1、Smad2、Smad3、Smad4、Smad7的mRNA和蛋白表达量。结果:与空白对照组比较,模型组超声结果从造模8周开始有明显差异,TGF-β1及Smad2、Smad3、Smad4、Smad7的mRNA和蛋白表达量从造模6周有非常明显差异;与模型对照组比较,给药组超声心电图各项结果均好转,给药组除小剂量组外心肌组织Ⅰ型胶原、Ⅲ型胶原、TGF-β1的表达水平均明显降低,治疗组TGF-β1、Smad2、Smad3、Smad4、Smad7的mRNA和蛋白表达量显著降低,差异均有统计学意义(P<0.05)。结论:抗纤益心方能够改善DCM大鼠心室重构,可能与调控TGF-β/Smads通路有关,并且在DCM造模6周时介入效果更佳。

Objective:To investigate the effect of Kangxian Yixin Recipe on dilated cardiomyopathy(DCM)model rats based on TGF-β1/Smads signaling pathway.Methods:The DCM rat model was prepared by furazolidone aqueous solution,and the successfully prepared model rats were randomly divided into the model control group,the low-dose Kangxian Yixin Recipe group(4.7 g·kg^(-1)),and the high-dose Kangxian Yixin Recipe group.(18.8 g·kg^(-1)),benazepril group(10.125 mg·kg^(-1)),combined drug group(Kangxian Yixin Recipe 18.8 g·kg^(-1)+benazepril 10.125 mg·kg^(-1)),different time of modeling group and blank control group.The modeling group at different time and the model control group were given furazolidone drinking water throughout the whole process.The administration group was given the corresponding drug from the 6th week of modeling,and the drug was administered continuously for 8 weeks.Rat echocardiography,the expression of collagenⅠ,Ⅲand TGF-β1 in myocardial tissue,RT-PCR and Western Blot methods were used to detect the mRNA and protein expression of TGF-β1,Smad2,Smad3,Smad4,Smad7 in myocardial tissue.Results:Compared with the blank control group,the ultrasound results of the model group were significantly different from the 8th week of modeling,and the mRNA and protein expressions of TGF-β1,Smad2,Smad3,Smad4,and Smad7 were significantly different from the sixth week of modeling.Compared with the model control group,the echocardiographic results of the rats in the administration group were improved.Except for the low-dose group,the expression levels of myocardial tissueⅠ,Ⅲcollagen and TGF-β1 in the rats in the administration group were higher than those in the model group.Compared with the model group,the mRNA and protein expression levels of TGF-β1,Smad2,Smad3,Smad4 and Smad7 in the myocardial tissue of the rats in the administration group were significantly lower.Conclusion:Kangxian Yixin Recipe can improve ventricular remodeling in DCM rats,which may be related to the regulation of TGF-β/Smads pathway,and the intervention effect is better when the DCM model is established for 6 weeks.