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目的探讨HepaRG细胞移植对鼠特异性Fas抗体诱导的急性肝衰竭小鼠的治疗作用和人肝细胞异种移植的策略。方法利用特异性鼠抗Fas抗体(Jo2mAb)腹腔注射,剂量为0.3mg/kg,诱导20只SCID小鼠制备急性肝衰竭模型,24h内按照实验动物随机数字表分组方法,经脾移植2×106HepaRG细胞的小鼠为实验组(10只),未经HepaRG细胞移植的小鼠为对照组(10只)。观察小鼠的存活率、肝脏功能、肝组织变化情况。实验组移植4周免疫组化检测肝组织人白蛋白、人CK18、人HepPar1的表达,免疫荧光检测人白蛋白的表达。结果实验组小鼠有9只存活超过4周,而对照组小鼠3d内先后死亡9只,实验组血清ALT和AST趋于正常,显著低于对照组(P<0.01),且存活时间显著高于对照组(P<0.01)。实验组经HepaRG细胞移植能避免Jo2mAb所致肝组织出血、坏死,移植后4周免疫组化可见人白蛋白、CK18、HepPar1阳性表达细胞,肝组织免疫荧光可见人白蛋白阳性细胞的表达。结论移植HepaRG细胞可治疗Jo2mAb腹腔注射小鼠诱导的急性肝衰竭,HepaRG细胞不仅在小鼠肝内存活,且得以增殖。
Objective To investigate the therapeutic effect of HepaRG cell transplantation on murine-specific Fas antibody-induced acute liver failure and the strategy of human hepatocyte xenotransplantation. Methods Acute liver failure model was induced in 20 SCID mice by intraperitoneal injection of specific anti-Fas antibody (Jo2mAb) at a dose of 0.3mg / kg. Within 24 hours, mice were randomly divided into two groups according to the random number table method: 2 × 106HepaRG The mice in the control group (10 mice) were used as the experimental group (10 mice) and the mice without the HepaRG cell transplantation (10 mice). Observe the survival rate of mice, liver function, liver tissue changes. At 4 weeks after transplantation, the expression of human albumin, human CK18 and human HepPar1 were detected by immunohistochemistry and the expression of human albumin was detected by immunofluorescence. Results Nine mice survived for more than 4 weeks in the experimental group and 9 died in the control group. The serum ALT and AST in the experimental group tended to be normal, significantly lower than that in the control group (P <0.01), and the survival time was significant Higher than the control group (P <0.01). The HepaRG cells were transplanted in the experimental group to prevent hemorrhage and necrosis of the liver tissue induced by Jo2mAb. The expression of human albumin, CK18 and HepPar1 were observed by immunohistochemistry 4 weeks after transplantation, and the expression of human albumin positive cells was observed by immunofluorescence. Conclusion Transplantation of HepaRG cells can treat acute hepatic failure induced by intraperitoneal injection of Jo2mAb in mice. HepaRG cells not only survive in the liver of mice, but also proliferate.