维生素D通过调控LKB1/AMPK/ACC信号通路缓解地塞米松诱导的骨骼肌萎缩
Vitamin D alleviates dexamethasone-induced skeletal muscle atrophy by regulating the LKB1/AMPK/ACC signaling pathway
申丽娟 1徐琪 1欧瑞燕 1吴疆 1李康1
作者信息
- 1. 深圳市龙岗区人民医院临床营养科,广东深圳 518172
- 折叠
摘要
目的 探讨维生素D通过调控LKB1/AMPK/ACC信号通路缓解地塞米松诱导的骨骼肌萎缩的分子机制.方法 通过C2C12诱导分化和地塞米松共孵育,构建体外肌管萎缩模型;通过小鼠腹腔注射地塞米松,构 建体 内骨骼肌萎缩模型;通过免疫荧光技术,考察体外肌管直径、肌管长度和肌管融合指数;通过免疫印迹技术,观察体内外模型中p-LKB1、p-AMPK、p-ACC、Atrogin 1等蛋白的表达水平;通过小鼠抓握力测试,考察维生素D对小鼠骨骼肌力的影响;通过HE染色,考察小鼠骨骼肌纤维的横截面积.结果 与对照组相比,地塞米松显著减小体内、外模型中的肌管直径、肌管长度、肌管融合指数和小鼠抓握力,显著提高了Atrogin1、MuRF1和Myostatin的表达水平,并显著抑制了LKB1/AMPK/ACC信号通路的活性(P＜0.01);与地塞米松处理组相比,维生素D显著改善了体内外模型中地塞米松诱导的骨骼肌萎缩,且具有剂量依赖性(P＜0.01).结论 维生素D通过调控LKB1/AMPK/ACC信号通路缓解地塞米松诱导的骨骼肌萎缩.
Abstract
Objective To investigate the molecular mechanism by which Vitamin D alleviates dexametha-sone-induced skeletal muscle atrophy by regulating the LKB1/AMPK/ACC signaling pathway.Methods An in vitro myotubular atrophy model was constructed by C2C12-induced differentiation and dexamethasone co-incubation;An in vivo skeletal muscle atrophy model was constructed by intraperitoneal injection of dexamethasone into mice;In vi-tro myotubular diameter,myotubular length and myotubular fusion index were examined by immunofluorescence tech-nique;p-LKB1,p-AMPK,p-ACC,p-AMPK,p-ACC and p-AMPK were examined by immunob1otting in the in vivo and in vitro models.The expression levels of p-LKB1,p-AMPK,p-ACC,Atrogin 1 and other proteins were investi-gated by immunoblotting;the effect of Vitamin D on skeletal muscle strength in mice was examined by mouse grasp strength test;the cross-sectional area of skeletal muscle fibres in mice was examined by HE staining.Results Com-pared with the control group,dexamethasone induction significantly reduced myotube diameter,myotube length,myotube fusion index and mouse grip strength in vivo and in vitro model,significantly increased the expression levels of Atrogin1,MuRF1 and Myostatin,and significantly inhibited the activity of LKB1/AMPK/ACC signaling pathway(P＜0.01);Compared with the dexamethasone treated group,Vitamin D-treated group significantly improved dexa-methasone-induced skeletal muscle atrophy in an ex vivo model in a dose-dependent manner(P＜0.01).Conclusion Vitamin D alleviates dexamethasone-induced skeletal muscle atrophy by regulating the LKB1/AMPK/ACC signaling pathway.
关键词
骨骼肌萎缩/维生素D/地塞米松/肝激酶B1Key words
Skeletal muscle atrophy/Vitamin D/Dexamethasone/Liver kinase B1(LKB1)引用本文复制引用
基金项目
深圳市龙岗区科技发展专项基金项目(LGWJ2021-033)
出版年
2024
NETL
NSTL
万方数据