芪苈强心胶囊通过TLR4/NF-κB通路减轻心力衰竭大鼠心肌炎性反应的研究

Study on Qiliqiangxin capsule attenuating myocardial inflammation in rats with heart failure through TLR4/NF-κB signaling pathway

目的探讨芪苈强心胶囊对心力衰竭大鼠心肌Toll样受体4(TLR4)/核因子-κB(NF-κB)信号通路及炎性细胞因子表达的影响。方法经尾静脉注射阿霉素2 mg/kg,1次/周,连续8周,建立大鼠心力衰竭模型。将大鼠分为对照组、心力衰竭组(HF组)及心力衰竭+芪苈强心胶囊组(HF+QLQX组)。对照组、HF组以蒸馏水10 mL·kg-1·d-1灌胃4周,HF+QLQX组采用1 g·kg-1·d-1芪苈强心胶囊药粉溶液灌胃4周。采用Western blot检测各组心肌细胞肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6、TLR4、NF-κB p65蛋白表达水平,TUNEL染色检测各组心肌细胞凋亡,苏木素-伊红染色检测各组心肌细胞形态学变化。结果HF组心肌细胞TNF-α、IL-1β、IL-6、TLR4、NF-κB p65表达水平较对照组明显增多(P<0.05),细胞凋亡率明显升高[(35.23±1.67)%vs.(1.63±0.26)%,P<0.05];与HF组比较,HF+QLQX组心肌细胞TNF-α、IL-1β、IL-6、TLR4、NF-κB p65表达水平明显减少(P<0.05),细胞凋亡率明显降低[(22.20±1.29)%vs.(35.23±1.67)%,P<0.05],心肌结构损伤减轻。结论芪苈强心胶囊可能通过TLR4/NF-κB信号转导通路减轻心力衰竭大鼠心肌细胞炎性反应和损伤。

Objective To investigate the effects of Qiliangxin capsule on myocardial Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway and inflammatory cytokine expression in rats with heart failure.Methods A model of heart failure in rats was established by intravenous tail injection of doxorubicin 2 mg/kg,once a week for 8 weeks.The rats were divided into the control group,the heart failure group(the HF group)and the heart failure+Qiliangxin capsule group(the HF+QLQX group).The control group and the HF group were intragastrically administered with distilled water 10 mL·kg-1·d-1 for 4 weeks.The HF+QLQX group was administered with 1 g·kg-1·d-1 Qiliangxin capsule solution for 4 weeks.The expressions of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6,TLR4 and NF-κB p65 in the myocardium were detected by Western blot,cardiomyocyte apoptosis was detected by TUNEL staining,and morphological changes of myocardium were detected by hematoxylin-eosin staining.Results The HF group showed higher levels of TNF-α,IL-1β,IL-6,TLR4,NF-κB p65 expression(P<0.05),and higher cardiomyocyte apoptosis rate[(35.23±1.67)%vs.(1.63±0.26)%,P<0.05]than the control group.Compared with the HF group,the expressions of TNF-α,IL-1β,IL-6,TLR4 and NF-κB p65 in the HF+QLQX group significantly decreased(P<0.05),the rate of cardiomyocyte apoptosis decreased[(22.20±1.29)%vs.(35.23±1.67)%,P<0.05],myocardial structural damage alleviated.Conclusion Qiliangxin capsule attenuates myocardial inflammation and injury in rats with heart failure through TLR4/NF-κB signaling pathway.