经脾脏hMSCs移植对乙酰氨基酚所致小鼠急性肝损伤的治疗作用

Curative effect of transsplenic human mesochymal stem cells transplantation on acetaminophen-induced acute liver injury in mice

目的:评价经脾脏途径行骨髓间充质干细胞(hSMCs)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,将SCID小鼠20只,随机分成2组,经脾脏注射组和对照组(n=10),经脾脏途径行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移植前后重症联合免疫缺陷病(severe combined immunodeficiency disease,SCID)小鼠肝腺泡结构的恢复与肝功能的改善情况.结果:SCID小鼠肝功能在经脾脏移植组与对照组相比较呈现显著性改善(28d时,ALT:26.3U/L vs 50.1U/L,P<0.01;AST:108.0U/L vs 154.3U/L,P<0.05;ALB:40.0g/L vs 31.9g/L,P<0.05).免疫荧光显示经脾脏移植的hMSCs在脾脏、肝脏均有较多量定植、分化与增殖.免疫荧光观察到脾脏移植后肝腺泡结构有较明显改善.结论:经脾脏途径行hMSCs移植能改善小鼠急性肝损伤肝功能,hMSCs在小鼠肝内生长良好,是hMSCs移植治疗的有效途径.

AIM： To assess efficacy of transsplenic human mesochymal stem cells （hMSCs） transplantation on acetaminophen-induced acute liver injury in mice. METHODS： An animal model of acetaminophen-induced acute liver injury was established. Twenty severe combined immunodeficiency mice （SCID mice） were randomly divided into 2 groups： transsplenic hMSCs transplantation group （n = 10） and control group （n = 10）. After transsplenic hMSCs transplantation, liver function test, immunofluorescence method, fluorescence microscopy and reticular fiber stainingwere performed to observe hepatic acinus and liver function of SCID rats. RESULTS： Liver function of SCID mice after transsplenic hMSCs transplantation was improved signif icantly compared with controls （at d 28, ALT： 26.3 U/L vs 50.1 U/L, P 〈 0.01; AST： 108.0 U/L vs 154.3 U/L, P 〈 0.05; ALB： 40.0 g/L vs 31.9 g/L, P 〈 0.05）. Fluorescence microscopy indicated hMSCs through transsplenic transplantation began to reside, differentiate and proliferate in spleen and liver in large number. Immunofluorescence method showed remarkable improvement of hepatic acinus following transsplenic hMSCs transplantation. CONCLUSION： Transsplenic hMSCs transplantation improves acute liver injury induced by acetaminophen in SCID mice and human mesochymal stem cells are able to proliferate in liver. Transsplenic transplantation is effective for hMSCs transplantation.