Smad7修饰的骨髓间充质干细胞对肝硬化大鼠治疗及其机制研究  

Experimental research of therapeutic effect of Smad7 gene modified bone marrow mesenchymal stem cells on liver cirrhosis rats

作　　者：苏冬娜[1] 吴诗品[1] 

机构地区：[1]深圳市人民医院暨南大学第二临床学院感染内科,深圳518020

出　　处：《中国免疫学杂志》2016年第5期692-696,共5页Chinese Journal of Immunology

基　　金：深圳市科创委立项课题20140320101246

摘　　要：目的:探讨Smad7修饰的骨髓间充质干细胞对肝硬化大鼠的治疗作用,并对相关机制进行研究,为临床治疗方法提供理论依据。方法:选取80只健康雄性Wistar大鼠,随机分为4组,对照组(C):不采取任何干预措施;肝硬化组(LC):行大鼠肝硬化模型制备;空载体转染组(Ad-e GFP-LC):行大鼠肝硬化模型制备后给予Ad-e GFP空载体修饰的骨髓间充质干细胞移植治疗;治疗组(Ad-Smad7-e GFP-LC):行大鼠肝硬化模型制备后给予Ad-Smad7-e GFP修饰的骨髓间充质干细胞移植治疗。取各组大鼠的肝脏组织,行HE染色。检测各组大鼠体重和肝湿重,血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总蛋白(TP)、白蛋白(Alb)含量以及肝组织TGFβ1、Smad3以及Smad7 mRNA表达量。结果:BMSCs移植入大鼠体内后,Ad-Smad7-e GFP-LC组大鼠肝脏组织病理学有明显改善,肝脏纤维化和干细胞变性坏死的程度明显降低;Ad-Smad7-e GFP-LC组大鼠体重低于C组(P<0.05),均高于Ad-e GFP-LC及LC组(P<0.05);Ad-Smad7-e GFP-LC组大鼠肝湿重高于C组(P<0.05),均低于Ad-e GFP-LC及LC组(P<0.05);Ad-Smad7-e GFP-LC组大鼠体内ALT、AST表达均高于C组(P<0.05),均低于Ad-e GFP-LC及LC组(P<0.05);Ad-Smad7-e GFP-LC组大鼠体内Alb及TP表达量低于C组(P<0.05),均高于Ad-e GFP-LC及LC组(P<0.05);Ad-Smad7-e GFP-LC组大鼠体内TGFβ1、Smad3 mRNA表达均高于C组(P<0.05),均低于Ad-e GFP-LC及LC组;Ad-Smad7-e GFP-LC组大鼠体内Smad7 mRNA表达量均高于C组,Ad-e GFP-LC及LC组(P<0.05)。结论:Smad7修饰的骨髓间充质干细胞移植入肝硬化大鼠体内可减轻疾病的发生,其机制可能与减弱TGFβ-Smad信号转导通路相关。Objective： To investigate the effect of Smad7 gene modified bone marrow mesenchymal stem cells（ BMSCs） on liver cirrhosis rats,thereby explaining the mechanism of immunoloregulation of BMSCs in vivo. Methods： 80 male Wistar rats were randomly divided into 4 groups,the control group（ C）,the liver cirrhosis group（ LC）,adenovirus Ad-e GFP transfected into liver cirrhosis group（ Ad-e GFP-LC）,and adenovirus Ad-Smad7-e GFP transfected into liver cirrhosis group（ Ad-Smad7-e GFP-LC）. And then detect HE staining,body weight and wet weight of liver; the expression of ALT,AST,TP,and Alb; the expression of TGFβ1,Smad3,and Smad7 mRNA in all groups. Results： HE staining showed that Ad-Smad7-e GFP-LCs group＇s amount of pseudolobules,degree of cell degeneration and adipose degeneration was the lowest under average visual fields. The body weight in Ad-Smad7-e GFP-LCs group was lower than that in C group（ P〈0. 05）,higher than that in Ad-e GFP-LC and LC group（ P 0. 05）; the wet weight of liver in Ad-Smad7-e GFP-LCs group was higher than that in C group（ P〈0. 05）,lower than that in Ad-e GFP-LC and LC group（ P〈0. 05）. The expression of ALT,and AST in Ad-Smad7-e GFP-LCs group was higher than that in C group（ P〈0. 05）,lower than that in Ad-e GFP-LC and LC group（ P〈0. 05）; the expression of Alb and TP in Ad-Smad7-e GFP-LCs group was lower than that in C group（ P 0. 05）,higher than that in Ad-e GFP-LC and LC group（ P〈0. 05）; the expression of TGFβ1 and Smad3 mRNA in Ad-Smad7-e GFP-LCs group was higher than that in C group（ P〈0. 05）,lower than that in Ad-e GFP-LC and LC group（ P〈0. 05）. The expression of Smad7 mRNA in Ad-Smad7-e GFP-LCs group was higher than that in C group,Ad-e GFP-LC and LC group（ P〈0. 05）. Conclusion： Smad7 gene modified BMSCs could reduce symptoms of liver cirrhosis rats,and the mechanism maybe involve the inhibition of the signal transduction pathway of TGFβ-Smad.

关 键 词：SMAD7 骨髓间充质干细胞 肝硬化 

分 类 号：R657.31[医药卫生—外科学]