五酯胶囊对他克莫司相关肝功能异常的影响及其与ABCB1基因多态性的关系

Effects of Wuzhi Capsules on tacrolimus-related hepatic dysfunction and its relationship with ABCB1 gene polymorphism

目的明确五酯胶囊对他克莫司相关肝功能异常的影响及其与ATP结合盒转运体B1(ABCB1)基因多态性的关系。方法选取联勤保障部队第九〇〇医院2014年11月至2018年3月接受肾移植、且术后应用他克莫司的受者170例,检测其ABCB1基因型,根据受者术后是否联用五酯胶囊分为研究组(105例)与对照组(65例),记录肾移植术后受者入院期间的用药情况、各项临床指标及他克莫司相关肝功能异常发生情况。比较两组受者及不同ABCB1基因型亚组间他克莫司相关肝功能异常发生率、类型及严重程度。结果两组受者间他克莫司相关肝功能异常发生率的差异无统计学意义(P>0.05)。对照组受者中,ABCB1 C1236T CC型受者的他克莫司相关肝功能异常发生风险为TT型受者的31.5倍(95%CI3.634~273.079,P=0.02),ABCB1 CGC单倍体携带者他克莫司相关肝功能异常的发生风险为非携带者的8.296倍(95%CI2.113~32.581,P=0.02)。而在研究组受者中则未发现类似情况。结论肾移植术后发生他克莫司相关肝功能异常的风险与ABCB1基因多态性显著相关,ABCB1 C1236T CC基因型及ABCB1 CGC单倍体携带型受者表现出更高的他克莫司相关肝功能异常发生风险,其机制可能与他克莫司代谢不充分从而在肝细胞内积蓄有关;五酯胶囊的应用可显著降低此类风险的发生。

Objective To explore the effects of Wuzhi Capsules on tacrolimus related hepatic dysfunction and examine its relationship with ATP-binding cassette subfamily Bmember 1(ABCB1)polymorphism.Methods From November 2014 to March 2018,a total of 170 patients undergoing renal transplantation were tested for ABCB1 genotype.They were divided into two groups of observation(n=105)and control(n=65)according to whether or not Wuzhi Capsules were taken postoperatively.The situations of medications,clinical parameters and tacrolimus related hepatic dysfunctions during hospitalization were recorded after transplantation.The incidence,type and severity of tacrolimus-related hepatic dysfunction were compared between two groups and different ABCB1 genotypes.Results No significant inter-group difference existed in the incidence of tacrolimus-related hepatic dysfunction(P>0.05).In control group,the risk of tacrolimus-related hepatic dysfunction was 31.5 folds in ABCB1 C1236T CC patients than that in TT(95%CI:3.634-273.079,P=0.02)and ABCB1 CGC haploid carriers had an 8.296 folds higher risk of tacrolimus-related hepatic dysfunction than non-carriers(95%CI:2.113-32.581,P=0.02).However,no similar case was found in observation group.Conclusions The risk of tacrolimus related hepatic dysfunction is significantly correlated with ABCB1 gene polymorphism duringhospitalizations in renal transplant patients.Recipients with ABCB1 C1236T CC genotype and ABCB1 CGC haploid have a higher risk of tacrolimus-related hepatic dysfunction.The mechanism may be correlated with insufficient metabolism of tacrolimus and its accumulation in hepatocytes.The application of Wuzhi capsules can significantly lower such risks.