门静脉输注骨髓干细胞诱导肝移植大鼠长期存活的实验研究

Inducing the Long-term survival of rat liver transplantation by recipient Mesenchymal stem cells engraftment in transplanted livers

目的探讨骨髓间充质干细胞诱导肝移植大鼠长期存活的机制。方法:24只受体Wistar大鼠随机分为A(正常对照)、B(D-hanks液)、C(间充质干细胞)3组,术后观察各组大鼠的生存时间、肝功能(ALT、TBil)和病理变化及Sry基因和白蛋白的表达状况。结果C组中位生存时间较A、B组显著延长(P<0.05);移植术后1周各组血清ALT、TBil均较正常值增高(P<0.05),C组明显低于A、B组(P<0.05);术后10天A、B组均呈急性中重度排斥反应,术后60天C组无明显的急性排斥反应。结论经门静脉输注的骨髓间充质干细胞在移植肝脏中逐渐分化为具有生物活性的肝细胞,可能是减轻急性排斥反应,导致大鼠长期存活的原因。

Objective To investigate the role of mesenchymal stem cells in the long-term survival of rat with liver transplantation Methods 24 recipient Wistar rats were divided into 3 groups: blank-control group (Group A), D-hanks solution group (Group B) and mesenchymal stem cells ( MSCs) group (Group C). The liver function (ALT、Tbil) were observed 1 week after the operation. Liver pathological changes and survival time were also observed. Liver repopulation and differentiation were assessed using Gene-Sry in site hybrid histochemistry(ISHH)and Albumin Immunohistochemistry (IHC). Results Compared with group A and B, The medium survival time of group C increased significantly (P<0.05).However, ALT, TBil decreased significantly (P<0.05). The group A and B showed more severe acute rejection in 10 days after the operation, but there was little evidence of acute rejection in group C 60 days later after the operation. Conclusions The reason of alleviating the acute rejection and improving the long-term survival of rat with liver transplantation might be the mesenchymal stem cells differentiation into bioactive hepatocytes gradually by intraportal transfusion.