uPA基因修饰骨髓源性肝干细胞移植对肝纤维化大鼠TGF-β-Smads信号通路的影响  

Effect of transplantation of uPA gene-modified bone marrow-derived liver stem cells on the TGF-β/Smad signal pathway in rats with liver f ibrosis

作　　者：孙超[1] 李定国[1] 陈源文[1] 陈颖伟[1] 汪保灿[1] 

机构地区：[1]上海交通大学医学院附属新华医院消化内科,上海市200092

出　　处：《世界华人消化杂志》2011年第8期789-793,共5页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.30500236;上海市教委科研基金资助项目;No.05BZ49;上海市教委优秀青年教师科研专项基金资助项目;No.jdy06040;上海市科委医学临床研究重点科技攻关基金资助项目;No.064119527~~

摘　　要：目的:探讨尿激酶型纤溶酶原激活物(uPA)基因修饰骨髓源性肝干细胞(BDLSC)移植对CCl4诱导的大鼠肝组织转化生长因子-β-Smads(TGF-β-Smads)信号通路的影响.方法:采用皮下注射CCl4建立大鼠肝纤维化模型.将纯系Fisher大鼠随机分为正常组、模型组、BDLSC组(尾静脉注入2×106BDLSC)和BDLSC-uPA组(尾静脉注入2×106AduPA转染的BDLSC),每组9只.观察各组大鼠肝功能和病理组织学变化;采用免疫组织化学法或Westernblot法分别检测大鼠肝组织TGF-β1、Smad3及Smad7蛋白表达变化.结果:与模型组和BDLSC组相比,BDLSC-uPA组大鼠肝脏结缔组织增生程度减轻,假小叶形成不明显,肝功能明显改善;肝组织TGF-β1蛋白表达明显低于模型组和BDLSC组(0.1849±0.0456vs0.8202±0.0636,0.2936±0.0548,均P<0.05),而Smad3和Smad7蛋白表达无明显变化.结论:uPA基因修饰BDLSC移植可能部分通过抑制TGF-β1蛋白表达,从而发挥抗肝纤维化的作用.AIM： To explore the effect of transplantation of urokinase-type plasminogen activator （uPA） gene-modified bone marrow-derived liver stem cells （BDLSC） on the transforming growth factor-β （TGF-β）/Smad signal pathway in ratswith CCl4-induced liver fi brosis.METHODS： Liver f ibrosis was induced in rats by subcutaneous injection of CCl4.The rats were ran- domly divided into control group,model group,BDLSC group （injected with 2×106 BDLSC via the tail vein）,and BDLSC-uPA group（injected with 2×106 uPA–transfected BDLSC via the tail vein）.Liver function and hepatic pathohistological changes were detected,and the expression of TGF-β1,Smad3 and Smad7 proteins was determined by immunohistochemistry or Western blot.RESULTS： In the BDLSC-uPA group,the extent of liver f ibrosis was much milder,the formation of pseudolobules was less obvious,liver function was better,and the expression of TGF-β1 protein in the liver （0.1849 ± 0.0456 vs 0.8202 ± 0.0636,0.2936 ± 0.0548,both P 〈0.05） was signif-icantly lower compared with the control group and BDLSC group.No signif icant difference was observed in the expression of Smad3 and Smad7 proteins among all the groups.CONCLUSION： Transplantation of uPA gene-modified BDLSC exerts an anti-fibrosis effect partly by inhibiting the expression of TGF-β1 protein.

关 键 词：尿激酶型纤溶酶原激活物 骨髓源性肝干细胞 肝纤维化 转化生长因子-β1 Smad3 SMAD7 

分 类 号：R575.2[医药卫生—消化系统]