基质金属蛋白酶2,9及金属蛋白酶组织抑制因子1,2在大鼠失神经骨骼肌的表达及意义  

Expression and effects of matrix metalloproteinase 2 and 9 and tissue inhibitor of metalloproteinase 1 and 2 in the denervated skeletal muscle of rats

作　　者：陈波[1] 梁杰[1] 陈振兵[2] Chen Bo;Liang Jie;Chen Zhen-bing(Department of Orthopedics,People’s Hospital of China Three Gorges University,Yichang 443000,Hubei Province,China;Department of Hand Surgery,Union Hospital,Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430022,Hubei Province,China)

机构地区：[1]三峡大学人民医院骨科,湖北省宜昌市443000 [2]华中科技大学同济医学院附属协和医院手外科,湖北省武汉市430022

出　　处：《中国组织工程研究》2018年第4期516-522,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金资助项目(81271967)~~

摘　　要：背景:基质金属蛋白酶及其组织抑制因子参与正常和病理情况下细胞外基质的重塑,研究表明基质金属蛋白酶2,9在骨骼肌损伤、失用等过程中都有表达,在其中具有重要的生理病理作用。目的:分析基质金属蛋白酶2,9及其组织抑制因子1,2在失神经骨骼肌中的表达及意义。方法:将大鼠右侧坐骨神经切断建立失神经骨骼肌模型,分别于术后不同时间段取右侧失神经的腓肠肌,采用苏木精-伊红染色、免疫组织化学染色、定量荧光检测技术检测大鼠骨骼肌组织形态学变化,并对比基质金属蛋白酶2,9及其组织抑制因子1,2的表达,与假手术组进行对照。结果与结论:(1)坐骨神经切断后腓肠肌出现萎缩纤维化的变化;(2)基质金属蛋白酶2和组织抑制因子2在3 d及56 d时出现双高峰,基质金属蛋白酶9在3 d及70 d时出现双高峰,而组织抑制因子1在3 d时达到高峰后逐渐下降至正常,无第2个高峰出现;(3)提示基质金属蛋白酶及其组织抑制因子参与失神经肌肉组织的变化,组织抑制因子1,2对重塑进程有保护作用。基质金属蛋白酶及其组织抑制因子在失神经骨骼肌退变的不同阶段为维持组织完整性发挥着重要作用。BACKGROUND:Matrix metalloproteinases(MMPs)and their tissue inhibitors(TIMP)are involved in the remodeling of extracellular matrix under normal or pathological conditions,and the positive expression of MMP-2 and MMP-9 has been shown to play important physiological and pathological roles in the denervated skeletal muscle.OBJECTIVE:To investigate the expression and effect of MMP-2 and MMP-9 and their tissue inhibitors(TIMP-1 and TIMP-2)in the denervated skeletal muscle.METHODS:The right sciatic nerve of rats was cut off to establish the model of denervated skeletal muscle,and the right skeletal muscle of rats was harvested after different intervals.The morphologic changes of the denervated skeletal muscle were detected through hematoxylin-eosin staining,immunohistochemical staining,and RT-PCR.The expression and change of MMP-2 and MMP-9 and TIMP-1 and TIMP-2 were compared with the sham operation group.RESULTS AND CONCLUSION:Atrophy and fibrosis were observed in the denervated skeletal muscle.There was a rapid increase of MMP-2 and TIMP-2 with double peaks at the 3rd and 56th days after modeling;at the 3rd and 70th days,the expression of MMP-9 increased significantly and reached the peak respectively;mRNA level of TIMP-1 only increased in the early stage,reached the peak at the 3rd day and gradual declined to normal level,without the second peak.To conclude,MMPs and TIMPs are involved in the tissue changes following denervation.TIMP-1 and TIMP-2 have a protective role in the remodeling progression.The altered balance between MMPs and TIMPs in the late stage of denervation may be responsible for extracellular matrix degradation leading to the atrophy and fibrosis progression.

关 键 词：失神经骨骼肌 萎缩 纤维化 基质金属蛋白酶2 基质金属蛋白酶9 金属蛋白酶组织抑制因子1 金属蛋白酶组织抑制因子2 国家自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]