自体骨髓细胞诱导肝移植大鼠长期存活的机制探讨

目的 研究自体骨髓细胞诱导肝移植大鼠长期存活的可能机制.方法 雌性受体大鼠随机分成空白对照组(A组)、D-hanks液组(B组)、全骨髓细胞组(C组)、间充质干细胞组(D组).观察大鼠的中位生存时间(median survival time,MST)、肝功能、病理变化、Sry基因原位杂交和甲胎蛋白、白蛋白免疫组化双标检测观察自体骨髓细胞的分化情况.结果 C组、D组MST均>180 d(P<0.01);血肝功能指标C组、D组降低明显,有显著差异(P<0.01);C组、D组之间比较无显著差异(P>0.05);移植术后60 d C、D组均无明显的急性排斥反应;C组、D组Sry基因原位杂交和甲胎蛋白、白蛋白免疫组化双标检测呈阳性.结论 自体骨髓细胞能减少排斥反应、诱导大鼠肝移植术后长期存活,其中间充质干细胞在移植肝内诱导分化为肝细胞发挥肝细胞功能,是其中可能的机制.

Long-term survival of rats using self bone marrow cell engraftment in transplanted livers after liver transplantation

Objective To investigate the mechanisms of the long-term survival rats after using self bone marrow cell engraftment in transplanted livers liver transplantation.Methods The female rats receiving orthotopic liver transplantation were randomized into the blank control group (Group A), D hanks solution group (Group B), whole bone marrow cell group (Group C) and mesenchymal stem cell (MSCs) group (Group D).The blood levels of alanine transaminase (ALT) and total bili ru-bin (TBil) were determined 1 week after the transplantation.Liver pathological changes and survival time were also analyzed.The differentiation of the self bone marrow cells were assessed 60 days after transplantation using in situ hybridization histochemistry (ISHH)for Sry gene and alpha fetoprotein (AFP) or albumin immunohistochemistry(IHC).Results As compared with group A and B, MST of group C and D was significantly increased(P<0.01).And no significant difference was found between group C and group D(P>0.05).As compared with group A and B, liver function 1 week after opera-tion was improved a lot in group C, D(P<0.01), and the difference between group C and group D was not statistically significant(P>0.05).The group A and B showed more serious acute rejection in 10 days after the operation, but there was little evidence of acute rejection in group C, D 60 days after the operation.ISHH for Sry gene and AFP or Albumin IHC double labeled cells were observed in group C and D.The percentage of the double staining positive ceils in group C was similar to that in group D(P>0.05).Conclusion Infusion of self bone marrow cells through the portal vein following liver transplantation could alleviate the acute rejection and induce long-term liver graft survival.MSCs can differentiate into hepatocytes expressing AFP or albumin.This may be the mechanism of the long-term liver graft survival.