脐带源间充质干细胞移植治疗肝纤维化及肝硬化的相关机制  

Human umbilical cord-derived mesenchymal stem cell tansplantation for liver fibrosis and cirrhosis

作　　者：孙慧聪[1] 张国尊[1] 郭金波[1] 冯燕[1] 郑力搏[1] 张晓岚[1] 

机构地区：[1]河北医科大学第二医院东院消化科,河北省石家庄市050000

出　　处：《中国组织工程研究》2015年第41期6638-6645,共8页Chinese Journal of Tissue Engineering Research

摘　　要：背景:肝硬化是多种原因引起的肝脏慢性病变,目前尚没有有效的治疗方法,很多研究表明,间充质干细胞对肝纤维化及肝硬化有一定的治疗作用。目的:研究人脐带源间充质干细胞移植对大鼠肝纤维化及肝硬化的治疗作用及其作用机制。方法:应用CCl4诱导制备肝纤维化及肝硬化模型,造模后经尾静脉注射人脐带间充质干细胞。细胞移植后采用Beckman Coulter analyzer检测人脐带源间充质干细胞移植对大鼠肝功能的影响;采用天狼猩红染色检测肝组织病理改变;应用免疫组织化学染色、Western blot和real-time Q-PCR方法检测Ⅰ、Ⅲ型胶原、基质金属蛋白酶2、基质金属蛋白酶抑制剂2蛋白与mR NA在大鼠肝组织中的表达。结果与结论:人脐带源间充质干细胞移植可以改善肝纤维化及肝硬化大鼠的肝功能。人脐带源间充质干细胞移植后,除肝纤维化细胞移植1周组与对应模型组相比差异无显著性意义外,其余各细胞移植组肝脏组织中基质金属蛋白酶2 mR NA及蛋白表达水平明显升高,而Ⅰ、Ⅲ型胶原、基质金属蛋白酶抑制剂2表达水平明显降低。人脐带源间充质干细胞通过上调基质金属蛋白酶2表达,下调基质金属蛋白酶抑制剂2表达,对肝纤维化及肝硬化起到治疗作用;在致病因素持续存在的情况下,人脐带源间充质干细胞移植并不能逆转肝纤维化或者肝硬化,只能延缓肝纤维化或肝硬化的进程。BACKGROUND： Cirrhosis is a long-term consequence of chronic hepatic injury, which has no effective therapy. Mesenchymal stem cells have been shown to play a potential role in the treatment of liver fibrosis/cirrhosis. OBJECTIVE： To investigate the therapeutic effect and mechanism of human umbilical cord-derived mesenchymal stem cells on CCl4 induced liver fibrosis/cirrhosis in rats. METHODS： A CCl4-induced liver fibrotic/cirrhotic rat model was used, and human umbilical cord-derived mesenchymal stem cells were injected via the tail vein after modeling. Liver biochemical profile was measured by Beckman Coulter analyzer. Histopathological changes were assessed by Sirius red staining. The expressions of collagen type I, collagen type III, matrix metalloproteinases-2 and tissue inhibitor of matrix metalloproteinases-2 protein and m RNA in liver tissues were observed by immunohistochemistry, western blot and real-time PCR, respectively. RESULTS AND CONCLUSION： Liver biochemical profile indicated the transplantation of human umbilical cord-derived mesenchymal stem cells could improve the liver function of rats with liver fibrosis and cirrhosis. After cell transplantation, except 1-week cell transplantation group, the expressions of the matrix metalloproteinases-2 m RNA and protein were significantly increased, while the expressions of collagen type I, collagen type III andtissue inhibitor of matrix metalloproteinases-2 m RNA and protein significantly decreased, compared with the corresponding model groups. Human umbilical cord-derived mesenchymal stem cells play a role in the treatment of liver fibrosis and cirrhosis through upregulating the expression of matrix metalloproteinases-2 and lowering the expression of inhibitor of matrix metalloproteinases-2. With the continued presence of pathogenic factors, human umbilical cord-derived mesenchymal stem cell transplantation cannot reverse liver fibrosis or cirrhosis, and only delay the process of liver fibrosis or cirrhosis.

关 键 词：肝硬化 间质干细胞 胶原Ⅰ型 胶原Ⅲ型 基质金属蛋白酶类 组织工程 干细胞 移植 肝纤维化 脐带间充质干细胞 Ⅰ型胶原 Ⅲ型胶原 MMP-2 TIMP-2 

分 类 号：R394.2[医药卫生—医学遗传学]