水杨酸盐激活AMPK-FoxO1途径诱导肌肉萎缩  

Salicylate induces skeletal muscle atrophy by activating AMPK and FoxO1

作　　者：赵彬佳惠 齐秀英[1] 吕晓红[1] 郑晓琳 赵加斌[2] ZHAO Bin-jia-hui;QI Xiu-ying;LU Xiao-hong;ZHENG Xiao-lin;ZHAO Jia-bin(Department of Anatomy,Harbin Medical University,Harbin 150081,China;Department of Emergency Surgery,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]哈尔滨医科大学解剖学教研室,黑龙江哈尔滨150081 [2]哈尔滨医科大学附属第一医院急诊外科,黑龙江哈尔滨150001

出　　处：《哈尔滨医科大学学报》2018年第6期525-529,共5页Journal of Harbin Medical University

摘　　要：目的探讨水杨酸盐对肌肉萎缩的影响。方法在细胞实验[小鼠成肌细胞(C2C12)]及动物模型(野生型小鼠)两个水平进行评定。将样本随机分为对照组及实验组,实验组给予水杨酸盐投药。投药后检测实验组细胞直径及测量小鼠肌肉重量,与对照组比较来评定是否发生肌肉萎缩,同时检测细胞及肌肉中萎缩标志物Atrogin1及MuRF1的表达,并检测AMPK通路中相关信号分子的表达水平。结果与对照组相比较,实验组的细胞直径以及肌肉组织重量显著降低,且萎缩标志物Atrogin1及MuRF1的mRNA表达明显上升,而炎症因子TNFα、IL1β、IL6的表达则明显下降。同时,实验组中磷酸化AMPK及FoxO1的蛋白表达均较对照组增加,而磷酸化mTOR的表达受到了抑制。结论水杨酸盐虽然抑制炎症因子的表达,但是激活了AMPK通路而导致肌肉萎缩。Objective To identify the role of salicylate on skeletal muscle atrophy.Methods The effect of salicylate on muscle atrophy was assessed by using C2C12 cells and wild-type mice with or without salicylate treatment.The muscle atrophied was determined by measuring cell diameter and muscle wet weight,the m RNA expression of genes related to muscle atrophy(e.g.Atrogin1,MuRF1 and so on) in cells and mice were examined.Furthermore,the proteins expression which involved in AMPK pathway was examined.Results Cell diameter and muscle mass were dramatically reduced in groups with salicylate treatment,accompanied by increased m RNA expression of Atrogin1,and MuRF1 which were closely related to muscle atrophy.In addition,inflammation cytokines TNFα,IL1β and IL6 mRNA expression was suppressed in mice dealt with salicylate.Moreover,protein expression level of phosphorylated AMPK and FoxO1 were increased and phosphorylated m TOR was reduced in cells and mice with salicylate treatment.Conclusion Although salicylate treatment represses the inflammation cytokines expression,it accelerates muscle atrophy by activating AMPK-FoxO1 pathway.

关 键 词：肌萎缩 水杨酸盐 AMPK FOXO1 MTOR 

分 类 号：R746.4[医药卫生—神经病学与精神病学]