经门静脉骨髓间充质干细胞移植治疗小鼠急性肝损伤的疗效

Experimental study of transplanting human mesenchymal stem cells via portal vein to treat acute liver injury of mice induced with acetaminophen

目的评价经门静脉途径行骨髓间充质干细胞（hMSCs）移植对对乙酰氨基酚所致小鼠急性肝损伤的疗效。方法建立对乙酰氨基酚导致的急性药物性肝损伤动物模型，经门静脉途径行hSMCs移植，采用肝功能检查、免疫荧光、荧光显微镜、网状纤维染色等方法观察hMSC移植前后严重联合免疫缺陷病小鼠肝腺泡结构的恢复与肝功能的改善情况。结果免疫缺陷病小鼠肝功能在经门静脉移植组与对照组比较明显改善（P〈0．05）。免疫荧光显示经门静脉移植的hMSCs在肝脏有大量定植、分化与增殖。免疫荧光观察到门静脉移植后肝腺泡结构改善明显。结论经门静脉途径的hMSCs移植能显著改善急性肝损伤小鼠肝功能，经门静脉移植的hMSCs在小鼠肝内生长良好，是hMSCs移植治疗的良好途径。

Objective To evaluate the effects of human mesenchymal stem cells （hMSCs） transplantation via portal vein to treat acute liver injury in mice induced with acetaminophen. Methods A model of acute liver injury was established by acetaminophen gavage with a dose of 500 mg/kg. Twenty severe combined immune deficient mice （SCID mice） were ramdomly divided into 2 groups; one with hMSCs transplantation via their portal veins, the other group served as controls and only saline was infused into their veins. Liver function tests, fluorescein staining and reticular fiber staining of liver histological preparations and fluorescence- and light-microscopy were applied to observe the biochemical and pathological changes in the mice before and after the transplantation of hMSCs. Results Liver function of the hMSCs group was significantly better than that of the controls （P 〈 0.05）. Fluorescence microscopy revealed that the hMSCs appeared in the areas of the periportal veins at first and then extented to the central vein areas; the reticular fiber staining indicated that hMSCs could repair the architecture of the hepatic acini. No prominant fibrosis and pseudolobules were found. Conclusions hMSCs transplantation via portal vein to SCID mice with acute liver injury induced by acetaminophen can improve their liver function effectively; hMSCs growth in their livers and acinus reconstruction can be affected. We think it is a good method to treat acute liver injury.