CYP2C19基因多态性对氯吡格雷在急性脑梗死治疗中抗炎作用的影响  

Effect of CYP2C19 gene polymorphism on the anti-inflammatory effect of clopidogrel in the treatment of acute cerebral infarction

作　　者：曹文达 姚利和 谷有全[2] CAO Wenda;YAO Lihe;GU Youquan(The First Clinical College of Medicine,Lanzhou University,Lanzhou 730030,China;Department of Neurology,The First Hospital of Lanzhou University,Lanzhou 730030,China)

机构地区：[1]兰州大学第一临床医学院,甘肃兰州730030 [2]兰州大学第一医院神经内科,甘肃兰州730030

出　　处：《陕西医学杂志》2025年第4期487-491,共5页Shaanxi Medical Journal

基　　金：甘肃省自然科学基金资助项目(22JR5RA941)。

摘　　要：目的:探究CYP2C19基因多态性对氯吡格雷在急性脑梗死(ACI)治疗过程中抗炎作用的影响。方法:收集125例服用氯吡格雷进行抗凝治疗的ACI患者为研究对象。测定患者CYP2C19基因表型和治疗前后血清超敏C反应蛋白(hs-CRP)、白细胞介素-1β(IL-1β)、IL-6、肿瘤坏死因子-α(TNF-α)。比较患者治疗前后及携带不同CYP2C19基因型患者血清hs-CRP、IL-1β、IL-6、TNF-α水平。结果:纳入125例患者中共检出71例CYP2C19*1/*1基因型,32例CYP2C19*1/*2基因型,9例CYP2C19*1/*3基因型,5例CYP2C19*2/*2基因型,3例CYP2C19*3/*3基因型,5例CYP2C19*2/*3基因型。基因表型以快代谢型为主,占比56.80%,其余为中间代谢型(32.80%)和慢代谢型(10.40%)。患者治疗后血清hs-CRP、IL-1β、IL-6、TNF-α水平较治疗前明显下降(均P<0.05)。携带快代谢型CYP2C19基因的ACI患者治疗前和治疗后血清hs-CRP、IL-1β、IL-6、TNF-α水平均低于携带中间代谢型、慢代谢型CYP2C19基因患者(均P<0.05),治疗前后血清hs-CRP、IL-1β、IL-6、TNF-α水平下降差值高于携带中间代谢型、慢代谢型CYP2C19基因患者(均P<0.05)。携带中间代谢型与慢代谢型CYP2C19基因的ACI患者治疗前、治疗后和治疗前后血清hs-CRP、IL-1β、IL-6、TNF-α水平差值间比较差异无统计学意义(均P>0.05)。结论:CYP2C19基因型在ACI患者中以快代谢型为主,CYP2C19基因型与机体炎症水平有关,氯吡格雷对快代谢型CYP2C19基因ACI患者具有更好的抗炎作用。Objective:To investigate the effect of CYP2C19 gene polymorphism on the anti-inflammatory effects of clopidogrel in the treatment of acute cerebral infarction(ACI).Methods:125 ACI patients taking clopidogrel for anticoagulant therapy were collected as subjects.CYP2C19 gene phenotype and serum hypersensitive C-reactive protein(hs-CRP),interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α)were determined before and after treatment.Serum levels of hs-CRP,IL-1β,IL-6 and TNF-αwere compared before and after treatment and in patients with different CYP2C19 genotypes.Results:Among the 125 patients,CYP2C19*1/*1 genotype was detected in 71 cases,CYP2C19*1/*2 genotype in 32 cases,CYP2C19*1/*3 genotype in 9 cases,CYP2C19*2/*2 genotype in 5 cases,CYP2C19*3/*3 genotype in 3 cases,CYP2C19*2/*3 genotype in 5 cases.The main gene phenotypes were fast metabolites(56.80%),the rest were intermediate metabolites(32.80%)and slow metabolites(10.40%).The serum levels of hs-CRP,IL-1β,IL-6 and TNF-αafter treatment were significantly decreased compared with those before treatment(all P<0.05).Serum hs-CRP,IL-1β,IL-6 and TNF-αlevels of ACI patients with fast metabolized CYP2C19 gene were lower than those of patients with intermediate metabolized and slow metabolized CYP2C19 gene before and after treatment(all P<0.05),and the serum hs-CRP,IL-1β,IL-6 and TNF-αlevels before and after treatment was higher than that of patients with intermediate metabolic type and slow metabolic type CYP2C19 gene(all P<0.05).There was no significant difference in serum hs-CRP,IL-1β,IL-6 and TNF-αlevels in ACI patients with intermediate and slow metabolized CYP2C19 genes before,after and before treatment(all P>0.05).Conclusion:The CYP2C19 genotype is mainly a fast metabolizing type in ACI patients,and the CYP2C19 genotype is related to the level of inflammation in the body.Clopidogrel has better anti-inflammatory effect in patients with fast metabolizing CYP2C19 gene ACI.

关 键 词：急性脑梗死 药物疗法 基因多态性 CYP2C19 氯吡格雷 抗炎 

分 类 号：R743.3[医药卫生—神经病学与精神病学]