黄芪多糖通过TLR4/NF-κB 信号通路抑制脂多糖诱导的大鼠心肌细胞肥大

摘要

Aim To explore the mechanism of Astrag-alus polysaccharide ( APS ) affecting lipopolysaccharide ( LPS )-indueed eardiae myocyles hypertrophy of rats from the aspect of TLR4-NF-ΚB signal transduction pathvvay. Methods The hypertrophie primary cardiac colls of nouonatal rats were induced by 1 mg · L-1 LPS, and the effect of different concentrations of APS and BAY 11-7082 ( IΚBα. phosphorylation inhibitor ) on cardiac hyperLrophy was observed. The cardiomyocyle volume was measured by compuLer phoLograph analysis system and the total protein content was assayed by the method of Bradford; the expression of TLR4, IΚBα. and TNF-α were determined by RT-PCR, Western blot and EL1SA, respectively. Results APS and BYA11- 7082 could inhibit the LPS-induced cardiac hypertrophy by reducing the cardiomyocyte protein content and volume; APS could abolish the inflammatory response induced by LPS in a dose-dependent manner, which was partially via attenuaLing IκBα and TMF-α signaling pathway. Conclusion APS has a protective effect on LPS-induccd cardiac hypertrophy , which is partially via at tenuating inflammatory through TLR4/NF-κB signaling pathway.%目的 旨在从TLR4-NF-κB信号转导通路角度探讨黄芪多糖(APS)对脂多糖(LPS)诱导新生大鼠心肌细胞肥大的作用机制.方法 原代培养新生大鼠心肌细胞,以LPS 1 mg·L-1诱导心肌细胞肥大,观察不同浓度APS及IκBα磷酸化抑制剂BAY11-7082对肥大心肌细胞的影响.以计算机图像分析系统检测细胞体积;考马斯亮蓝法测定细胞总蛋白含量;RT-PCR法检测TLR4 mRNA的表达;Western blot法检测心肌细胞 IκBα 的蛋白表达;ELISA法检测细胞外液TNF-α 的含量.结果 APS及BAY11-7082均能有效抑制LPS诱导的心肌肥大,表现为蛋白含量降低,体积减小;并能有效减少炎症反应,表现为TLR4 mRNA表达降低,IκBα的蛋白含量升高,细胞外液中TNF-α明显减少,且APS的作用呈一定的剂量依赖性.结论 黄芪多糖对LPS诱导的乳鼠心肌细胞有保护作用,其机制可能与抑制TLR4/NF-κB信号通路有关.