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

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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(n 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,n 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,n P=0.02)。而在研究组受者中则未发现类似情况。n 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 B member 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 (n 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,n 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, n P=0.02). However, no similar case was found in observation group.n 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.
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