MMP1过表达的骨髓间充质干细胞对肝纤维化的修复作用  

Therapeutic ef ect of BMSCs with over-expressed MMP1 on liver i brosis

作　　者：魏晓龙[1] 蒋明德[2] 曾维政[2] 郑淑梅[2] 汤善宏[2] 杜超[2] 

机构地区：[1]第三军医大学研究生管理大队,重庆400038 [2]成都军区总医院消化内科,成都610083

出　　处：《中南大学学报（医学版）》2014年第3期258-264,共7页Journal of Central South University ：Medical Science

摘　　要：目的:探讨基质金属蛋白酶1(matrix metalloproteinase 1,MMP-1)过表达的骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)对大鼠肝纤维化修复作用的影响。方法:50只雄性SD大鼠随机分为4组,重组腺病毒Ad-人MMP-1(human MMP-1,hMMP-1)-增强绿色荧光蛋白(enhanced green fluorescent protein,EGFP)组(A组,n=10)、空载体Ad-EGFP组(B组,n=10)、肝纤维化对照组(C组,n=15)及正常对照组(D组,n=15)。应用CCl4植物油溶液皮下注射制作大鼠肝纤维化模型,10周后成模。经尾静脉将已转染的细胞注入大鼠体内,肝纤维化对照组和正常组注射等量生理盐水。3周后处死大鼠,观察转染MMP-1的BMSCs对大鼠体质量、肝组织质量、肝功能、肝纤维化指标及肝组织病理的影响。结果:与对照组相比,转染MMP-1的BMSCs致大鼠体质量、肝组织质量和血清白蛋白显著增加(P<0.05);血清谷丙转氨酶(ALT)、总胆红素(TBIL)、透明质酸酶(hyaluronic acid,HA)、层粘连蛋白(laminin,LN)及III型前胶原(procollagen III,PC III)显著下降(P<0.05);苏木精-伊红染色法(HE染色)可见平均视野下纤维化的程度显著改善(P<0.05)。结论:转染hMMP-1能够增强BMSCs对肝纤维化的修复能力。Objective: To investigate the function of bone marrow mesenchymal stem cells(BMSCs) with over-expressed matrix metalloproteinase 1(MMP1) on liver i brosis. Methods: Fit y SD male rats were randomly divided into 4 groups: recombinant adenovirus Adhuman MMP-1(hMMP-1)-enhanced green fluorescent protein(EGFP) transfected BMSCs group(Group A, n=10), Ad-EGFP transfected BMSCs group(Group B, n=10), liver fibrosis group(Group C, n=15), and a normal group(Group D, n=15). h e liver i brosis model was formed by subcutaneous injection of the mixed liquor of carbon tetrachloride(CCL4) and vegetable oil. At er10 weeks, the model of liver i brosis was formed. Group A and B were administered the transfected BMSCs via the tail veins, while Group C and D were administered normal saline. At er 3 weeks, the rats were sacrii ced. h e body weight, liver weight, liver function, liver i brosis indexes and liver pathological changes were tested. Results: Compared with the control group, the rats administered BMSCs with over-expressed MMP1 showed a significant improvement in the body weight, liver weight and plasma albumin(ALB)(P<0.05), and a signii cant reduction in the plasma alanine aminotransferase, total bilirubin, hyaluronic acid, laminin and procollagen III(P<0.05). Hematoxylin-eosin staining coni rmed that the degree of liver i brosis was signii cantly ameliorated under average visual i elds(P<0.05). Conclusion: h e repair ability of BMSCs on liver i brosis can be enhanced by over-expression of hMMP-1.

关 键 词：BMSCS 基质金属蛋白酶1 基因治疗 肝纤维化 

分 类 号：R575.2[医药卫生—消化系统]