TLR4/NF-κB信号通路在黄芪甲苷抑制异丙肾上腺素诱导大鼠心肌肥厚中的作用  

The Effect of TLR4/NF-κB Signaling Pathway on Astragaloside IV Inhibiting Myocardial Hypertrophy Induced by Isoproterenol in Rats

作　　者：杨娟[1,2] 王洪新[1] 张英杰[2] 李胜陶[1] 鲁美丽[1] 张静[1] 张素萍[1] 

机构地区：[1]辽宁医学院心血管药物研究重点实验室,辽宁省锦州市121001 [2]辽宁医学院第一附属医院心内科,辽宁省锦州市121001

出　　处：《中国动脉硬化杂志》2013年第7期577-582,共6页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金(30973898/C190702)项目;辽宁省自然科学资金(201102141)项目

摘　　要：目的探讨TLR4/NF-κB信号通路在黄芪甲苷抑制异丙肾上腺素诱导大鼠心肌肥厚中的作用。方法以异丙肾上腺素5 mg/(kg·d)腹腔注射制备大鼠心肌肥厚模型。60只SD大鼠随机分为6组,每组10只:正常对照组、异丙肾上腺素组、异丙肾上腺素+黄芪甲苷20 mg/(kg·d)、异丙肾上腺素+黄芪甲苷40 mg/(kg·d)、异丙肾上腺素+黄芪甲苷80 mg/(kg·d)及异丙肾上腺素+普萘洛尔40 mg/(kg·d)。给药组连续灌胃3周,并于灌胃1天后腹腔注射异丙肾上腺素2周。给药3周后,分别检测各组大鼠全心质量指数(HMI)、左心质量指数(LVMI);取左心室组织进行HE染色,测量左心室心肌细胞横径;RT-PCR检测心肌组织ANP和TLR4的mRNA表达;Western blot检测心肌组织TLR4、p65和IκBα的蛋白表达;ELISA检测血清中TNF-α、IL-6含量。结果同正常对照组相比,异丙肾上腺素组大鼠表现为HMI和LVMI显著增加,左心室心肌细胞横径增加,ANP和TLR4 mR-NA表达增加,TLR4和p65蛋白含量增加以及IκBα蛋白含量减少,血清中TNF-α、IL-6含量明显增加。与异丙肾上腺素组相比,黄芪甲苷不同剂量组表现为HMI和LVMI降低,左心室心肌细胞横径缩小,ANP和TLR4 mRNA表达减少,TLR4和p65蛋白含量减少以及IκBα蛋白含量增加,血清中TNF-α、IL-6含量减少,且呈一定的剂量依赖性。结论黄芪甲苷对异丙肾上腺素诱导的心肌肥厚有保护作用,其机制可能与抑制TLR4/NF-κB信号通路有关。Aim To observe the effect of TLR4/NF-κB signaling pathway on astragaloside IV inhibiting myocardial hypertrophy induced by isoproterenol （ISO）. Methods The ISO [5 mg/（kg·d）] was used as myocardial hypertrophy models by intraperitoneal injection. Sixty SD rats were randomly assigned to the following six groups （10 rats for each group）： normal group, ISO group, ISO plus astragaloside IV 20 mg/（kg·d） group, ISO plus astragaloside IV 40 mg/（kg·d） group, ISO plus astragaloside IV 80 mg/（kg·d） group, ISO plus propranolol 40 mg/（kg·d） group. Administered groups received continually intragastric administration for 3 weeks, and ISO were intraperitoneal injected as long as 2 weeks in the day after that. 3 weeks later, heart mass index （HMI） and left ventricular mass index （LVMI） of rats in each group were measured. HE staining was used for measuring transverse diameter of left ventricular myocardial cells （TDM）. RT-PCR was used to quantify mRNA expression of ANP and TLR4, Western blot was used to quantify protein expression of TLR4, p65 and IκBα in the tissue, ELISA was used to quantify TNF-α and IL-6. Results Comparing the ISO group with the normal group, the differences were in the followings： the HMI and LVMI were significantly increased, the TDM were increased, the protein expression of TLR4 and p65 were increased, while the IκBα were decreased the expression of TLR4 and ANP mRNA were increased, TNF-α and IL-6 in serum were significantly increased. Comparing the other 3 groups （ISO plus astragaloside IV） with the ISO group, the differences were in the followings： the HMI and LVMI were significantly decreased, TDM were decreased, the protein expression of TLR4 and p65 were decreased, while the IκBα were increased;the expression of TLR4 and ANP mRNA were decreased, TNF-α and IL-6 in serum were significantly decreased, and the differences were positively related to dose of three groups. Conclusions astragaloside IV has a protective effect on cardiac hypertro

关 键 词：黄芪甲苷 异丙肾上腺素 心肌肥厚 TLR4 NF—κB信号通路 

分 类 号：R363[医药卫生—病理学]