基于TGF-β1/Smad3信号通路观察促血小板生成素对阿霉素致心力衰竭大鼠心肌细胞凋亡的影响

Effects of thrombopoietin on adriamycin-induced cardiomyocyte apoptosis in rats with heart failure based on the TGF-β1/Smad3 signaling pathway

目的探讨促血小板生成素(TPO)对阿霉素致心力衰竭(CHF)大鼠抗心肌细胞凋亡的作用以及其对TGF-β1/Smad3信号的调控机制。方法将大鼠随机分为对照组、模型组、治疗组、抑制剂组;模型组、治疗组、抑制剂组采用腹腔注射阿霉素构建心衰模型,治疗组每日腹腔注射5μg/kg TPO;抑制剂组每日腹腔注射1. 2 mg/kg SB431542、TUNEL染色、免疫荧光、Western blot检测大鼠心肌细胞的凋亡、Caspase-3、TGF-β1及p-Smad3的表达水平。结果与对照组相比,模型组心肌细胞凋亡率、TGF-β1、p-Smad3、Caspase-3的表达明显升高,与模型组相比,治疗组、抑制剂组心肌细胞凋亡率、TGF-β1、p-Smad3、Caspase-3的表达明显降低,差异均具有统计学意义(P<0. 05)。结论 TPO能够降低由阿霉素导致CHF大鼠的心肌细胞凋亡率,其机制可能与抑制TGF-β1/Smad3信号有关。

Objective To investigate the effects of thrombopoietin on adriamycin-induced cardiomyocyte apoptosis in rats with heart failure based on the TGF-β1/Smad3 signaling pathway. Methods Rats were randomly divided into control,model,treatment,and inhibitor groups. Rats in the model,treatment,and inhibitor groups were injected with doxorubicin to establish a rat heart failure model. Rats in the treatment group were intraperitoneally injected with 5 μg/kg thyroperoxidase( TPO) daily and rats in the inhibitor group were intraperitoneally injected with 1. 2 mg daily/kg SB431542.TUNEL staining,immunofluorescence,and western blot were used to detect the cell apoptosis of cardiomyocytes,and the expressions of caspase-3,TGF-β1,and p-Smad3. Results Compared with the control group,the cell apoptosis rate of myocardial tissue cells in the model group was significantly increased and the expressions of TGF-β1,p-Smad3 and caspase-3 were significantly increased. Compared with the model group,the apoptosis rate of myocardial tissue in the treatment and inhibitor groups and the expressions of TGF-β1,p-Smad3,and caspase-3,were significantly decreased. The differences were statistically significant compared with the model group( P < 0. 05). Conclusions TPO reduced the apoptosis rate of cardiomyocytes induced by doxorubicin in rats. The mechanism may be related to the inhibition of the TGF-β1/Smad3 signaling pathway.