AMPK激活剂AICAR对矽肺大鼠肌成纤维细胞转化的调节机制  

AMPK ACTIVATOR AICAR INHIBITS MYOFIBROBLASTS DIFFERENTIATION IN SILICOTIC RATS

作　　者：阚泉 张岩 王海涛 李冉 阮向华 田艳霞 KAN Quan;ZHANG Yan;WANG HaiTao;LI Ran;RUAN Xianghua;TIAN Yanxia(Department of Histology and Embryology,North China University of Science and Technology,Tangshan 063000,China)

机构地区：[1]华北理工大学基础医学院组胚教研室,河北省唐山市063000 [2]华北理工大学附属医院

出　　处：《中国煤炭工业医学杂志》2021年第4期347-350,共4页Chinese Journal of Coal Industry Medicine

基　　金：河北省卫生厅医学科学研究课题计划(编号:20130380);唐山市科技局科学技术研究与发展计划(编号:13130291z)。

摘　　要：目的探讨AMPK激活剂AICAR对矽肺大鼠肌成纤维细胞转化的抑制机制。方法采用支气管灌注构建矽肺大鼠模型,实验分为对照组、矽肺模型组、AICAR预防组;体外原代培养大鼠肺成纤维细胞,实验分组为对照组、TGF-β1诱导组、AICAR组和TGF-β1+AICAR组。免疫组织化学染色观察α-SMA的阳性表达,免疫印迹法检测Col I、α-SMA、p-AMPK、AMPK的表达。结果与对照组比较,矽肺模型组Col I、α-SMA表达上调,而p-AMPK表达下调,予以AICAR预处理能够显著上调p-AMPK的表达,而抑制Col I、α-SMA、SRF的表达;与对照组比较,TGF-β1能够显著上调Col I、α-SMA、SRF表达的表达,而抑制p-AMPK的表达,予以AICAR预处理能够显著下调Col I、α-SMA、SRF的表达,而上调p-AMPK的表达。结论AICAR能够通过激活AMPK从而抑制矽肺大鼠肌成纤维细胞转化。Objective To explore the mechanism of AICAR,an AMPK activator,on inhibiting of myofibroblasts differentiation in silicotic rats.Methods SiO2 powders were instilled in the trachea of rat to make the silicotic model.Rats were divided into 3 groups,including control,silicosis,and AICAR pre-treatment group.Rat lung fibroblasts were divided into 4 groups,including control,TGF-β1,AICAR,TGF-β1+AICAR group.The positive expression ofα-SMA was observed by IHC staining.The expression of Col I、α-SMA、SRF、p-AMPK、AMPK were measured by western blot.Results Compared with control group,silica could significantly increase the levels of Col I、α-SMA、SRF in rats exposed to silica,accompanied with reducing of p-AMPK.Pre-treatment with AICAR reversed the changes induced by silica in rats.TGF-β1 increased the levels of Col I、α-SMA、SRF and decreased p-AMPK in fibroblsts.Treatment with AICAR also inhibited myofibroblasts differentiation in TGF-β1-treated fibroblasts by activating of p-AMPK.Conclusion AICAR can inhibit myofibroblsts differentiation in silicotic rats by activating of AMPK signaling.

关 键 词：矽肺 肌成纤维细胞转化 AICAR AMPK 

分 类 号：R13[医药卫生—劳动卫生]