缺血再灌注损伤介导MRP2表达下调对DCD供体肝移植术后胆红素代谢的影响

Downregulation of MRP2 Expression on Bilirubin Metabolism after Liver Transplantation from DCD Donors

目的探讨多耐药相关蛋白2 (MRP2)与肝移植术后缺血再灌注损伤的关系及胆红素升高的原因及其作用机制。方法监测24例肝移植患者术前及术后胆红素水平,光镜及电镜分析冷缺血及再灌注后移植肝细胞形态变化及胆红素颗粒的分布,使用RT-PCR检测肝组织MRP2在冷缺血及再灌注后表达变化。结果高胆红素血症在肝移植术后早期出现,以直接胆红素血症为主(P <0.05)。光镜及电镜下检测胆红素颗粒在肝细胞内的聚集,而肝细胞外的胆管内未见胆红素颗粒增多,术后供体肝组织中MRP2的m RNA水平较术前显著降低(P <0.001)。结论肝移植术后早期可出现胆红素升高,以直接胆红素升高为主;胆汁淤积位于肝细胞内而胆管内未见,其原因与缺血再灌注损伤介导的MRP2表达降低有关。

Objective To study the relationship between the multi-drug resistance related protein 2(MRP2) and ischemia-reperfusion injury and the cause and mechanism of high bilirubin after the liver transplantation.Method The preoperative and postoperative bilirubin levels of 24 liver transplantation patients were monitored.Light microscope and electron microscope analysis of cold ischemia and reperfusion after the transplantation of liver cell morphological changes and bilirubin granules distribution, RT-PCR were used to detect the liver tissue MRP2 expression changes after cold ischemia and reperfusion. Results Hyperbilirubinemia, dominated by direct bilirubinemia, appeared within 14 days after the liver transplantation(P<0.05). The increase of bilirubin was dominated by the increase of direct bilirubin(P<0.05). No extracellular biliary stasis was observed by light microscopy and electron microscopy after the liver transplantation,and MRP2 m RNA level in donor liver tissue was significantly lower after the operation than that before the operation(P < 0.001).Conclusion Hyperbilirubinemia, mainly direct bilirubinemia, can occur within 14 days after the liver transplantation.Cholestasis is present in the hepatocytes but not in the bile ducts after the liver transplantation, the reason is related to the decreased expression of MRP2 affected by ischemia-reperfusion injury.