益心泰醇提物对阿霉素致慢性心力衰竭兔TGF-β1/Smad3信号通路相关因子表达的影响

Effects of Yixintai Alcohol Extract on Expressions of TGF-β1/Smad3 Signaling Pathway Related Factors in Rabbits with Adriamycin-induced Chronic Heart Failure

目的观察益心泰醇提物对阿霉素致慢性心力衰竭(CHF)兔TGF-β1/Smad3信号通路相关因子表达的影响,探讨其作用机制。方法采用阿霉素耳缘静脉注射建立CHF兔模型,将成模兔随机分为对照组、模型组、氯沙坦钾组(2.73 mg/kg)及益心泰醇提物低、中、高剂量组(1.77、3.54、7.08 g/kg),分别给予相应药物灌胃,模型组和对照组予等体积蒸馏水灌胃,1次/d,连续4周。超声心动仪检测兔左室射血分数(LVEF);ELISA检测兔血清N末端B型利钠肽原(NT-proBNP)、血管紧张素Ⅱ(AngⅡ)含量;TUNEL染色法检测兔心肌细胞凋亡率;Western blot检测兔心肌组织Bax、Bcl-2、转化生子因子β1(TGF-β1)、Smad3、Ⅰ型胶原(CollagenⅠ)、Ⅲ型胶原(CollagenⅢ)蛋白表达。结果与对照组比较,模型组兔LVEF明显降低(P<0.01),血清NT-proBNP、AngⅡ含量明显增加(P<0.01),心肌细胞凋亡率明显升高(P<0.01),心肌组织Bax、TGF-β1、Smad3、CollagenⅠ、CollagenⅢ蛋白表达明显升高,Bcl-2蛋白表达明显降低(P<0.01);与模型组比较,益心泰醇提物各剂量组兔LVEF明显升高(P<0.05),血清NT-proBNP、AngⅡ含量明显减少(P<0.05,P<0.01),心肌细胞凋亡率明显降低(P<0.05,P<0.01),心肌组织Bax、TGF-β1、Smad3、CollagenⅠ、CollagenⅢ蛋白表达降低,Bcl-2蛋白表达升高,其中益心泰醇提物高剂量组差异有统计学意义(P<0.05,P<0.01)。结论益心泰醇提物可能通过调节TGF-β1/Smad3信号通路,改善兔心肌纤维化,抑制心肌细胞凋亡,从而发挥治疗CHF作用。

Objective To explore the effects of Yixintai alcohol extract on expressions of TGF-β1/Smad3 signaling pathway related factors in rabbits with adriamycin-induced chronic heart failure(CHF);To discuss its mechanism of action.Methods A rabbit model of CHF was established by intravenous injection of doxorubicin in the ear.The successful CHF model of rabbits were randomly divided into control group,model group,losartan group(2.73 mg/kg)and Yixintai alcohol extract low-,medium-,high-dosage group(1.77,3.54,7.08 g/kg).The corresponding drugs were given by gavage,and the model group and the control group were given an equal volume of distilled water by gavage,once a day,for 4 consecutive weeks.Echocardiography was used to detect the LVEF;ELISA was used to detect the contents of NT-proBNP and AngⅡin serum;TUNEL staining was used to detect cardiomyocyte apoptosis;Western blot was used to detect proteins expression of Bax,Bcl-2,TGF-β1,Smad3,CollagenⅠand CollagenⅢin myocardial tissue.Results Compared with the control group,the LVEF in the model group decreased(P<0.01);the contents of NT-proBNP and AngⅡin serum increased(P<0.01);the apoptosis rate of cardiomyocyte increased(P<0.01);the proteins expression of Bax,TGF-β1,Smad3,CollagenⅠand CollagenⅢin myocardial tissue increased,while the protein expression of Bcl-2 decreased(P<0.01).Compared with the model group,the LVEF in each dosage of Yixintai alcohol extract group increased(P<0.05);the contents of NT-proBNP and AngⅡin serum reduced(P<0.05,P<0.01);the apoptosis rate of cardiomyocyte was significantly decreased(P<0.05,P<0.01);the proteins expression of Bax,TGF-β1,Smad3,CollagenⅠand CollagenⅢin myocardial tissue decreased,while the protein expression of Bcl-2 increased,and the difference in Yixintai alcohol extract high-dosage group was stastically significant(P<0.05,P<0.01).Conclusion Yixintai alcohol extract could improve rabbit myocardial fibrosis and inhibit myocardial cell apoptosis by regulating the TGF-β1/Smad3 signaling pathway,so as to play a role in treating CHF.