黄芪甲苷抑制心肌肥厚的机制与TLR-4/NF-κB信号通路相关  

Astragaloside IV inhibits myocardial hypertrophy via TLR-4/NF-κB signaling pathway

作　　者：何海洋 王洪新 张晶 喻晓春[2] 

机构地区：[1]辽宁省心脑血管药物基础研究重点实验室,辽宁锦州121001 [2]中国中医科学院医学实验中心,北京100700

出　　处：《中成药》2013年第6期1111-1116,共6页Chinese Traditional Patent Medicine

基　　金：国家自然基金资助项目(30973898/C190702);辽宁省自然科学基金资助项目(201102141)

摘　　要：目的探讨黄芪甲苷对大鼠心肌肥厚的抑制作用是否与TLR-4/NF-κB信号转导途径有关。方法采用腹主动脉缩窄方法制备大鼠心肌肥厚模型,40只大鼠随机分为5组:假手术组、心肌肥厚模型组(模型组)、黄芪甲苷低剂量组[40 mg/(kg.d)]、黄芪甲苷高剂量组[80 mg/(kg.d)]、辛伐他丁组,每组8只。检测全心质量指数(HMI)、左心室质量指数(LVMI),显微镜下测量左心室心肌组织细胞横径大小,ELISA法检测血清中肿瘤坏死因子α(TNF-α)和白介素1β(IL-1β)水平,RT-PCR法检测心房利钠肽(ANP)及Toll样受体-4(TLR-4)mRNA的表达,West-ern bolotting检测NF-κB的蛋白表达。结果腹主动脉缩窄组的HMI、LVMI、细胞横径的大小、血清中TNF-α和IL-1β的水平、ANP mRNA、TLR-4 mRNA及NF-κB蛋白的表达均比假手术组有明显升高。与模型组相比,黄芪甲苷低剂量组的上述指标略有降低,高剂量组下降得更为显著。结论黄芪甲苷抑制炎症因子(TNF-α、IL-1β)/TLR-4/NF-κB通路的信号转导可能是其抑制心肌肥厚的作用机制之一。AIM To investigate the influence of astragaloside IV on rats with myocardial hypertrophy whether or not being related to TLR-4/NF-κB signaling pathway.METHODS Forty rats with myocardial hypertropy were established by abdominal aortic constriction and then divided into five groups（each group of 8 only）,which were sham,model,astragaloside IV low dose [40 mg/（kg·dheart mass index（HMI） and the left ventricular mass index（LVMI） in rats were weighted.The trans diameter of myocardial cell（TDM） was measured with the help of micrography.Then serum TNF-α and IL-1β levels were detected by ELISA.mRNA levels of atrial natriuretic peptide（ANP） and Toll-like receptor 4（TLR-4） were tested by RT-PCR,and protein expression of NF-κB was tested by Western bolotting.RESULTS The HMI,LVMI and TDM in the model group were higher than those in the sham group.The serum TNF-α and IL-1β mRNA levels of ANP and TLR-4,protein expression of NF-κB in model group were higher than those in the sham group.Compared with the model group,those indexes slightly decreased in astragaloside IV low dose group and obviously decreased in astragaloside IV high dose group.CONCLUSION The experiment shows that astragaloside IV inhibits myocardial hypertrophy via the（TNF-α,IL-1β）/TLR-4/NF-κB signaling pathway.

关 键 词：黄芪甲苷 心肌肥厚 TLR-4 NF-ΚB 肿瘤坏死因子Α 

分 类 号：R285.5[医药卫生—中药学]