心脏营养素-1对失神经骨骼肌的营养和保护作用  

The myotrophic and protective effect of Cardiotrophin-1 on denervated skeletal muscle

作　　者：马学晓[1] 张高孟[1] 冯勇[1] 顾玉东[1] 顾建新[2] 

机构地区：[1]复旦大学附属华山医院手外科,上海200040 [2]上海复旦大学上海医学院基因中心

出　　处：《中华手外科杂志》2006年第2期112-115,共4页Chinese Journal of Hand Surgery

基　　金：国家自然科学基金(30170964)

摘　　要：目的探讨心脏营养素-1(Cardiotrophin-1,CT-1)及其受体在失神经骨骼肌中的表达规律,观察外源性CT-1对失神经骨骼肌的营养和保护作用。方法选用11组Swiss小鼠,每组10只,切断其右侧胫神经,分别于术后不同时间点完整切取失神经腓肠肌,用Northern blot法测定肌肉中CT-1及其受体亚基LIFR-β,gp130的mRNA含量,探讨三者的表达规律。另取Swiss小鼠30只,同样方法切断其胫神经后,连续腹腔注射CT-1(100μg/kg/d),于7、14和28 d后检测失神经腓肠肌的湿重、肌纤维横截面积和肌肉总蛋白含量,观察超微结构的变化,分别与对照组比较。结果CT-1及其受体在正常骨骼肌中均有表达。胫神经切断后,腓肠肌中CT-1的表达进行性下降；而LIFR-β和gp130在早期均有一个表达增高的过程,前者的表达高峰出现在失神经支配后24 h,后者在神经切断后1周表达最高。连续应用外源性CT-1 2周,有效地维持了失神经腓肠肌的湿重、肌纤维横截面积和总蛋白含量,减轻了肌浆网的扩张程度。用药4周后,这种效果更加明显。结论内源性CT-1表达不足,是失神经骨骼肌早期萎缩的一个重要因素。受体gp130/LIFR-β的表达上调,提高了肌肉对其配体CT-1的敏感性,及时应用外源性CT-1,可对失神经骨骼肌产生营养和保护作用,能有效地延缓失神经骨骼肌的萎缩。Objective To investigate the expression patterns of cardintrophin-1 （CT-1） and its receptor in denervated muscles, and identify the potential myotrophic effect of CT-1 on skeletal muscle postdenervation. Methods 110 mice were randomly divided into 11 groups, whose right tibial nerves were transected. The expression of CT-1 and its receptor in gastrecnemius muscle was assayed using Northern blot analysis 0 hour, 6 hours, 12 hours, 1 day, 3 days, 5 days, 7 days. 10 days. 14 days, 21 days, and 28 days after denervation. Another 30 mice in three groups were intraperitoneally injected rmCT-1 （100μg/kg/d） after the tibial nerve was transected. Gastrecnemius muscles of the mice were isolated 7 days, 14 days, and 28 days postdenervation respectively. The changes of wet weight, crosssectional area, total protein, and ultrastructure of the denervated muscle were detected. All the results were compared with those of control groups. Results CT-1 and its receptor were both expressed in normal skeletal muscle and showed their own expression patterns with denervation time. Expression of CT-1 declined gradually, whereas two components of the receptor, leukemia inhibitory factor-β （LIFR-βand glycoprotein 130 （gp130）, were both augmented in the initial postdenervation phase. Daily administration of exogenous CT-1 for 2 weeks better sustained the wet weight, cross-sectional area, total protein of denervated muscles, and alleviated the dilation of sarcoplasmie reticulum. This effect was even more prominent after four weeks of administration. Conclusion Reduced expression of endogenous CT-1 in skeletal myecytes and its diminished myotrophic effect contributes to the early atrophy of denervated muscles. The up-regulated expression of the receptor allowed denervated muscle to be more responsive to exogenous CT-1. When administered in time, exogenous CT-1 would produce remarkable myotrophic and protective effect on denervated muscles, and alleviate denervation atrophy of skeletal muscles.

关 键 词：肌萎缩 去神经支配 肌 骨骼 心脏营养素-1 

分 类 号：R651.3[医药卫生—外科学] R746.4[医药卫生—临床医学]