猕猴自体骨髓CD133^+细胞肝门静脉移植治疗肝损伤的实验研究  

Therapeutic Values of Portal Application of Autologous Marrow Stem Cells for Treatment of Liver Necrosis in Monkey

作　　者：侯宝华[1] 潘兴华[2] 庞荣清[2] 和占龙[3] 张步振[2] 简志祥[1] 孙建[1] 区金锐[1] 

机构地区：[1]广东省人民医院肝胆外科,广州510080 [2]成都军区昆明总医院医学实验科,昆明650032 [3]中国医学科学院协和医科大学昆明医学生物研究所,昆明650032

出　　处：《热带医学杂志》2006年第5期527-529,F0004,共4页Journal of Tropical Medicine

基　　金：广东省自然科学基金博士启动项目(No.5300816);云南省自然科学基金重点项目(No.2003C013Z)

摘　　要：目的探讨自体CD133+细胞肝门静脉移植对猕猴肝损伤的治疗意义,为人类肝损伤治疗提供新技术。方法猕猴每日皮下注射40%CCL40.5ml/kg复制肝损伤模型后连续饲喂高脂饲料,经肝功能生化指标检测及肝穿组织病理学观察确认肝损伤后,免疫磁珠法分离自体骨髓CD133+细胞,按3×105细胞/kg将细胞植入肝门静脉,植入后60d进行肝功能相关指标检测及组织病理学观察。结果连续注射CCL44d后,血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、球蛋白(GLOB)均显著升高,而总蛋白(TP)和白蛋白含量无变化(P>0.05),肝组织结构紊乱,部分肝细胞水肿、变性和坏死,汇管区及周围有大量炎性细胞浸润。第二次肝门静脉细胞移植后30d,血清AST、ALT活性和GLOB、BIL含量显著低于对照组(P<0.05),而TP、ALB、LDL含量高于对照组(P<0.05),治疗组肝组织结构清楚,而对照组有部分纤维增生和肝细胞有脂肪变性。结论自体CD133+细胞肝门静脉移植能有效促进肝损伤修复和阻止猕猴肝损伤的发展,改善猕猴肝组织结构和功能。Objective To confirm the therapeutic values of portal application of autologous CD133^＋ cells for the treatment of liver necrosis in monkey and to establish new methods for the treatment of human liver disease. Methods Monkeys of 7-10 years old were induced to develop liver necrosis by subcutaneous injection with 40% CCL4 （0.5 ml/kg） daily for 4 days. After liver function and histological analysis, the animals were randomly divided into experimental and control groups. For the experimental group, CD133^＋ cells （3×10^5 cells/kg） were transplanted into liver by portal injection. The same number of CD133^＋ ceils was transplanted in the same way at 30 days after the first transplantion. The activity of liver enzymes, proteins, lipids and bilirubin content in plasma, and histological changes were determined 60 days after transplantation. Results Hepatoeyte degeneration and necrosis were observed 4 days after CCL4 injection. GLOB, TBIL, ALT and AST activities were increased（P〉0.01）. TP, ALB, and HDL contents were not changed （P〉0.05）in plasma. Hepatocyte degeneration, necrosis, coagulation, fibrosis and immunocytes infiltration were seen in the control group 60 days after CD133^＋ cell transplantaion. Mononuclear cells were also found to infiltrate around the duct area. Normal structure was found in the group with transplantation. ALT and AST activity, GLOB, TBIL, and TBA contents in plasma were signifieandy lower（P〈0.05） while TP,ALB, and HDL contents in plasma were higher than the control animals （P〈0.05）.Conelusion Autologous CD133^＋ ceil transplantation can effectively support hepatic regeneration in monkey with liver necrosis.

关 键 词：猕猴 肝损伤 骨髓干细胞 移植 

分 类 号：R575[医药卫生—消化系统]