微囊化猪肝细胞移植治疗大鼠急性肝衰的免疫隔离机制

Immunoisolation effects of microencapsulated porcine hepatocyte transplantation in treating acute hepatic failure in rats

目的:探讨微囊化猪肝细胞腹腔内移植对药物性肝衰大鼠的治疗作用,观察受体存活率、肝组织病理变化及大网膜的免疫隔离作用. 方法:以海藻酸钠-多聚赖氨酸-海藻酸钠(APA)包裹乳猪肝细胞,体外观察APA微囊对NK细胞介导的细胞毒作用的隔离效果.D-氨基半乳糖腹腔内注射诱导大鼠急性肝衰竭,48 h后将微囊化的猪肝细胞移植于大鼠腹腔内,观察移植大鼠存活率,免疫组化法检测大鼠大网膜内CD4、CD8、IgG和IgM的表达. 结果:微囊可有效保护囊内K562细胞不受NK细胞的杀伤.与裸肝细胞移植组相比,微囊化乳猪肝细胞移植组大鼠存活率显著提高(1wk存活率78.6% vs 66.7%, P=0.0 046;2 wk存活率42.9% vs 25.0%,P=0.0027, P<0.01).大网膜CD4、CD8、IgG表达较弱(P=0.0 342、P=0.0 197及P=0.0 445,P<0.05),而IgM表达无明显差异(P>0.05). 结论:APA微囊可有效隔离抗体及淋巴细胞介导的体液和细胞免疫反应.微囊化异种肝细胞移植可治疗大鼠急性肝衰,给予肝功能代谢支持,提高移植治疗效果.

AIM: To investigate the therapeutic effect of microencap-sulated porcine hepatocyte transplantation intraperito-neally on toxic hepatic failure in rats. METHODS: The isolated hepatocytes were encapsulated by the alginate method.The immunoisolation effects of sodium alginate-polyserine-sodium alginate (APA)microcapsules against NK cell-meidated cytotox-icity were evaluated. Microencapsulated porcine hepatocytes were transplanted into abdominal cavity of rats 48 hours after the induction of acute hepatic failure(AHF) with D-galactosamine. The survival rate and hepatic pathologic changes were determined. The expression of CD4, CD8, IgG and IgM in the greater omentum was examined. RESULTS: Microcapsules effectively protected K562 cells against the killing by NK cells. Compared with the free hepatocyte transplantation group, the survival rate of the rats in microencapsulated porcine hepatocyte transplantation group was significantly higher, and the expression of CD4, CD8 and IgG in the greater omen-tum was much weaker. CONCLUSION: APA microencapsules can effectively prevent cellular and humoral immune responses. Microen-capsulated xenogeneic hepatocyte stransplantation is effective in the treatment of AHF.