Chiu King-Wah, Nakano Toshiaki, Tseng Hui-Peng, Cheng Yu-Fan, Jawan Bruno, Eng Hock-Liew, Goto Shigeru, Chen Chao-Long
Kaohsiung Chang Gung Memorial Hospital, Taiwan, Republic of China.
Hepatogastroenterology. 2012 May;59(115):805-8. doi: 10.5754/hge09722.
The cytochrome P450 (CYP) drug-metabolizing enzymes play an important role in cellular metabolism. Therapeutic failure or drug toxicity in the period after liver transplantation (LT) is influenced by the drug metabolizing capacity of the graft. The expression levels of CYP2C19 enzyme are often used as an indicator of the functioning of the CYP system. The aim of the present study was to assess the CYP2C19 protein expression in the setting of living donor liver transplantation (LDLT) by using western blotting analysis.
We performed CYP2C19 genotyping of liver biopsy samples obtained from 24 donors and 8 recipients each in the pre- and post-LT periods, after which we analyzed the CYP enzyme activity by using western blotting analysis.
The CYP2C19/β-actin ratio, which was an indicator of CYP expression, was 61.75% (23-100%) in donors, 59.13% (15-100%) in pre-LT recipients and 46.71% (12-67%) in post-LT recipients (p>0.05). The CYP2C19 expression levels associated with different genotypes were as follows: homozygous extensive metabolizers (HomEMs; n=24), 56.63±24.74%; heterozygous extensive metabolizers (HetEMs; n=15), 63.0±25.14% and poor metabolizers (PMs; n=1), 82.0% (p>0.05).
Western blotting analysis showed low CYP2C19 protein expression not only in samples from the pre- and post-LT recipients but also from the donors.
细胞色素P450（CYP）药物代谢酶在细胞代谢中起重要作用。肝移植（LT）后出现的治疗失败或药物毒性受移植物的药物代谢能力影响。CYP2C19酶的表达水平常被用作CYP系统功能的指标。本研究的目的是通过蛋白质印迹分析评估活体肝移植（LDLT）情况下CYP2C19蛋白的表达。
我们对24例供体和8例受体在LT术前和术后获取的肝活检样本进行了CYP2C19基因分型，之后通过蛋白质印迹分析来检测CYP酶活性。
作为CYP表达指标的CYP2C19/β-肌动蛋白比率在供体中为61.75%（23 - 100%），LT术前受体中为59.13%（15 - 100%），LT术后受体中为46.71%（12 - 67%）（p>0.05）。与不同基因型相关的CYP2C19表达水平如下：纯合广泛代谢者（HomEMs；n = 24），56.63±24.74%；杂合广泛代谢者（HetEMs；n = 15），63.0±25.14%，以及慢代谢者（PMs；n = 1），82.0%（p>0.05）。
蛋白质印迹分析显示，不仅LT术前和术后受体的样本中CYP2C19蛋白表达较低，供体样本中也是如此。
