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  

Inhibition of Astragalus polysaccharide in lipopolysccharide-induced cardiomyocyte hypertrophy in rats through the TLR4/NF-κB signal transduction

作　　者：孙雪芳[1] 王洪新[1] 梁灵君[1] 鲁美丽[1] 顾洁莹[1] 何海洋[1] 

机构地区：[1]辽宁医学院心脑血管药物重点实验室,辽宁锦州121001

出　　处：《中国药理学通报》2013年第2期208-212,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30973898/C190702);辽宁省自然科学资金资助项目(No 201102141)

摘　　要：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 1mg.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。Aim To explore the mechanism of Astragalus polysaccharide（APS） affecting lipopolysaccharide（LPS）-induced cardiac myocytes hypertrophy of rats from the aspect of TLR4-NF-κB signal transduction pathway.Methods The hypertrophic primary cardiac cells of neuonatal rats were induced by 1 mg·L^-1 LPS,and the effect of different concentrations of APS and BAY11-7082（IκBα phosphorylation inhibitor） on cardiac hypertrophy was observed.The cardiomyocyte volume was measured by computer photograph 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 ELISA,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 attenuating IκBα and TNF-α signaling pathway.Conclusion APS has a protective effect on LPS-induced cardiac hypertrophy,which is partially via attenuating inflammatory through TLR4/NF-κB signaling pathway.

关 键 词：黄芪多糖 脂多糖 心肌细胞肥大 TLR4 NF—κB 炎症因子 TNF—α 

分 类 号：R-332[医药卫生] R284.1