肝移植术后黄疸患者肝组织的胆汁酸外排转运蛋白的表达

Expression of bile acid efflux transporters in liver tissue of jaundice patients after liver transplantation

目的通过病例对照研究检测和分析胆汁酸外转运蛋白BSEP、MRP2、MDR3在肝移植术后并发黄疸患者肝组织中的表达,探讨胆汁酸代谢在肝移植术后肝内胆汁淤积发生和发展中作用。方法收集2006-2017年南京军区福州总医院25例肝移植术后发生黄疸并行肝穿刺的患者的临床资料及肝脏穿刺活检组织的蜡块,进行组织学及相关蛋白的免疫组织化学检查(肝移植组),另收集同期血管瘤患者瘤旁正常组织18例作为对照组。应用免疫组织化学方法检测BSEP、MRP2、MDR3在病例组和对照组肝组织中的表达,采取半定量分析的方法,对比观察上述胆汁酸外转运蛋白在对照组、肝移植组及各病因导致的肝移植术后黄疸的肝组织中的表达差异。结果BSEP、MRP2、MDR3在肝移植术后黄疸的肝组织中的总体表达水平较对照组均下降(P均<0.05),但不同病因之间存在差别:BSEP仅在肝移植术后排斥反应、病毒性因素及胆管阻塞等病因所致黄疸的肝组织中的表达较对照组下降,差异具有统计学意义(分别为P<0.001、P=0.002、P=0.035);MRP2仅在病毒性因素所致肝移植术后黄疸的肝组织中的表达较对照组表达下降(P=0.012);而MDR3在肝移植术后排斥反应(P=0.001)、缺血再灌注损伤(P=0.011)、药物毒物(P=0.047)及阻塞性因素(P=0.013)所致移植后黄疸的肝组织中的表达较对照组存在统计学差异。结论肝移植术后黄疸患者肝组织中胆汁酸外排转运蛋白BSEP、MRP2、MDR3蛋白的表达水平的下调提示其可能在肝移植术后胆汁淤积的发病机制中起着重要的作用,但不同病因所致者的表达水平之间存在差别。

Objective This case control study aimed to detect and analyze the expression of bile acid transporters BSEP,MRP2,MDR3 in liver tissues of patients with jaundice after liver transplantation,and to explore the role of bile acid metabolism in its generation and development.Methods In the case control study,25 cases with jaundice and liver puncture after liver transplantation in Nanjing Military Area Command Fuzhou General hospital form 2006 to 2017 were selected.18 cases with hepatic hemangioma were selected as control group.Clinic data and paraffin block of liver biopsy tissue were collected on all patients.The liver specimens were performed for histopathological and immunohistochemical examinations.Immunohistochemistry was performed to detect the expression of BSEP,MRP2 and MDR3 in the liver tissues of two groups.Semi-quantitative analysis was applied to compare the expression difference of the above bile acid transporters in liver tissues of control group,the liver transplantation group and the jaundice group after liver transplantation caused by various causes.Results The total expression level of BSEP,MRP2 and MDR3 in jaundice liver tissue after liver transplantation was lower than that of the control group(P<0.05),but there is a difference between different causes:only the expression of BSEP in the liver tissues with jaundice caused by rejection,viral factors and bile duct obstruction after liver transplantation was significantly lower than that in the control group(P<0.001,P=0.002,P=0.035).MRP2 expression in liver tissues with jaundice caused by viral factors was lower than that in the control group.The expression of MDR3 in the liver tissues with jaundice caused by post-transplantation rejection(P=0.001),ischemia-reperfusion injury(P=0.011),drug toxicants(P=0.047)and obstructive factors(P=0.01)was significantly higher than that in the control group.Conclusion The down-regulated of bile acid efflux proteins BSEP,MRP2 and MDR3 in the liver tissue of patients with jaundice after liver transplantation suggested that they may play an important role in the pathogenesis of cholestasis after liver transplantation,but the expression levels of above-mentioned proteins in patients with different etiologies are different.