五酯胶囊和CYP3A5*3多态性与肾移植术后早期他克莫司血药浓度相关性研究

Association of wuzhi capsule and CYP3A5*3 genetic polymorphism with tacrolimus blood concentration of renal transplant recipients during the early stage after transplantation

目的探究五酯胶囊联合CYP3A5*3多态性对肾移植受者术后早期他克莫司血药谷浓度(trough concentration,C0)的影响。方法通过聚合酶链反应-限制性片段长度多态性法(polymerase chain reaction-restriction fragement length polymorphism,PCR-RFLP)测定CYP3A5*3基因型。利用化学发光免疫分析法(chemiluminescence immunoassay,CMIA)法测定他克莫司C0。分析五酯胶囊不同日剂量(dose,D)及CYP3A5*3基因型对肾移植受者术后早期他克莫司剂量调整血药谷浓度(dose-adjusted trough concentration,C0/D)的影响。结果五酯胶囊各日剂量组(0、22.5和45 mg)在术后第3、7和14天,CYP3A5表达者(*1/*1+*1/*3)的他克莫司C0/D显著低于非表达者(*3/*3)(P<0.05)。CYP3A5表达者在第3、7和14天,五酯胶囊各组(0、22.5和45 mg)的C0/D有显著性差异(P<0.05)。然而,第14天CYP3A5表达者五酯胶囊67.5 mg组的C0/D却显著低于22.5 mg和45 mg组(P>0.05),且CYP3A5非表达者五酯胶囊45 mg组的C0/D显著低于22.5 mg组(P<0.05)。结论CYP3A5表达的肾移植受者术后早期可联用五酯胶囊(最大日剂量44.5 mg),用于提升他克莫司浓度和降低药费。

Objective To investigate the effect of wuzhi capsule combined with CYP3A5*3 genetic polymorphism on the tacrolimus blood trough concentration(C0)of renal transplant recipients in the early post transplant stage.Methods CYP3A5*3 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Tacrolimus C0 was tested using chemiluminescence immunoassay(CMIA).The effect of both the daily dose(D)of wuzhi capsule and CYP3A5*3 genotype on the tacrolimus dose-adjusted trough concentration(C0/D)was evaluated in the early post transplant stage.Results Among all of the different wuzhi capsule groups(0,22.5 and 45 mg),tacrolimus C0/D of CYP3A5 expressers(*1/*1+*1/*3)was significantly lower than that of non-expressers(*3/*3)on day 3,7 and 14 after renal transplantation(P<0.05).In CYP3A5 expressers on day 3,7 and 14,there were significant differences of tacrolimus C0/D among different wuzhi capluse groups(0,22.5 and 45 mg).However,on day 14,tacrolimus C0/D with 67.5 mg wuzhi capsule group was significantly lower than those of both 22.5 mg and 45 mg groups(P>0.05),and tacrolimus C0/D with 45 mg group was significantly lower than that of 22.5 mg group(P>0.05).Conclusion For renal transplant recipients with CYP3A5 express,wuzhi capsule could be used to increase the blood concentration of tacrolimus and reduce its costs in the early stage after transplantation.