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PPARδ激动剂GW501516调节小鼠骨骼肌线粒体生物合成和纤维类型转换的作用 被引量:4

A primary investigation on the modulation of PPARδ agonist GW501516 on mitochondrial biogenesis and muscular fiber types in mice
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摘要 目的观察和比较PPARδ激动剂GW501516补充和(或)耐力训练对骨骼肌内源性PPARδ及PGC-1α表达、骨骼肌线粒体生物合成和骨骼肌肌纤维类型的影响。方法♂C57BL/6小鼠随机分为5组:正常对照组(C)、耐力训练组(T)、低剂量GW501516组(LG,3mg·kg-1·d-1,po)、低剂量激动剂干预+训练组(TG)、高剂量GW501516组(HG,10mg·kg-1·d-1,po)。15周实验期结束后,取腓肠肌以Western blot法测定骨骼肌组织PPARδ、PGC-1α、COXⅣ和MHCⅠ、MHCⅡ以及MHCⅡa蛋白表达;骨骼肌ATP酶染色区分纤维类型以及透射电镜观察。结果①与C、T组比较,电镜下可见激动剂干预各组(LG、TG)线粒体数目明显增多,排列整齐;②T、LG和TG组腓肠肌PPARδ、PGC-1α和COXⅣ蛋白表达量均较C组提高,且激动剂和训练在3种指标变化中均有交互作用;③小鼠腓肠肌ATP酶染色发现,与C组相比,T组的Ⅰ型肌纤维比例无变化;LG、TG组的Ⅰ型肌纤维增加,尤其以TG组明显;④T、LG、TG组的腓肠肌MHCⅡa蛋白表达量较C组提高,LG、TG组腓肠肌MHCⅡ蛋白表达量较C组降低的同时表现出MHCI蛋白的明显增加。激动剂和耐力训练在小鼠腓肠肌MHCs蛋白含量变化中有交互作用。结论①耐力训练与补充GW501516均可诱导骨骼肌线粒体生物合成;②GW501516补充可促进骨骼肌纤维类型由Ⅱ型向Ⅰ型的转变,单纯运动训练未发生肌纤维类型的转变;③GW501516补充与训练结合,在上调骨骼肌线粒体生物合成及肌纤维类型转变的过程中有叠加作用。 Aim To investigate the relationship of PPARδ,PGC-1αand mitochondrial biogenesis.Using GW501516,a selective agonist of PPARδ,the process of mitochondrial biogenesis induced by endurance training and/or supplying GW501516,and the shift from typeⅡto typeⅠof mice skeletal muscle were observed and compared.Methods Five groups of male C57BL/6 mice were compared:normal control(C) ,treadmill training(T) ,low dose GW501516(3 mg· kg -1 ·d -1,po) supplement(LG) ,high dose GW501516(10 mg·kg-1·d-1,po) supplement(HG) ,low dose GW501516 and training(TG) . GW501516 was added to drinking water.After 15 weeks,mice's gastrocnemius muscles were collected and tested according to the following parameters:transmission EM observation;protein expression of PPARδ,PGC-1α,COXⅣ,MHCⅠ,MHCⅡa and MHCⅡby Western blot;tissue staining to distinguish muscular fiber types.Results The transmission EM photos of mice's gastrocnemius showed that the mitochondrial number in groups with supplement of GW501516 was increased more than that in groups with no supplement(C and T) .The protein expression levels of PPARδ,PGC-1αand COXⅣin mice muscle of T,LG and TG groups were found to be much higher than those in C group.Both in T,LG and TG groups,the protein expression levels of MHCⅡa in mice muscle were higher than those in C group,and in LG and TG groups,the protein expression levels of MHCⅡwere low.In morphological observation,metachromatic staining revealed a muscle fiber transformation.In gastrocnemius muscle,it was estimated that there was a significant increase of typeⅠfibers in TG group.On all those parameters mentioned above,supplying GW501516 and training exhibited additional enhancing effects.Conclusions Both long-term endurance exercise and supplement of GW501516 can advance mitochondrial biogenesis in skeletal muscle,however,the shift of skeletal muscle typeⅡto typeⅠis a result of systemic changes triggered by PPARδ's agonist GW501516,and the muscular mitochondrial biogenesis induced by the interaction between PPARδand PGC-1αfinally leads to the shift of muscle types.
出处 《中国药理学通报》 CAS CSCD 北大核心 2010年第10期1290-1295,共6页 Chinese Pharmacological Bulletin
基金 国家自然科学基金资助项目(No30470837) 天津市社会发展重大科技攻关资助项目(No05YFGDSF02100)
关键词 PPARΔ GW501516 PGC-1Α 线粒体 生物合成 肌纤维类型 PPARδ GW501516 PGC-1α mitochondrial biogenesis muscle fiber types
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