[1]曹文达,姚利和,谷有全.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[J].陕西医学杂志,2025,54(4):487-491.[doi:DOI:10.3969/j.issn.1000-7377.2025.04.010]
　CAO Wenda,YAO Lihe,GU Youquan.Effect of CYP2C19 gene polymorphism on the anti-inflammatory effect of clopidogrel in the treatment of acute cerebral infarction[J].,2025,54(4):487-491.[doi:DOI:10.3969/j.issn.1000-7377.2025.04.010]
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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
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年4期
页码:
487-491
栏目:
临床研究
出版日期:
2025-04-05

文章信息/Info

Title:
Effect of CYP2C19 gene polymorphism on the anti-inflammatory effect of clopidogrel in the treatment of acute cerebral infarction
作者:
曹文达1; 姚利和2; 谷有全2
(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)
Author(s):
CAO Wenda1; YAO Lihe2; GU Youquan2
(1.The First Clinical College of Medicine,Lanzhou University,Lanzhou 730030,China; 2.Department of Neurology,The First Hospital of Lanzhou University,Lanzhou 730030,China)
关键词:
急性脑梗死;  药物疗法;  基因多态性;  CYP2C19;  氯吡格雷;  抗炎
Keywords:
Acute cerebral infarction;  Drug therapy;  Gene polymorphism;  CYP2C19;  Clopidogrel;  Anti-inflammatory
分类号:
R 743.3
DOI:
DOI:10.3969/j.issn.1000-7377.2025.04.010
文献标志码:
A
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。
Abstract:
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-α were 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-α after treatment were significantly decreased compared with those before treatment(all P<0.05).Serum hs-CRP,IL-1β,IL-6 and TNF-α levels 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-α levels 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-α levels 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.

参考文献/References:

[1] 李青松,杨言府,谢道俊,等.辛温开窍方治疗急性脑梗死临床研究[J].陕西中医,2024,45(3):331-334.
[2] PILON D,NESLUSAN C,ZHDANAVA M,et al.Economic burden of commercially insured patients with major depressive disorder and acute suicidal ideation or behavior in the united states[J].J Clin Psychiatry,2022,83(3):40440-40453.
[3] HUANG P,HE X,XU M.Effect of argatroban injection on clinical efficacy in patients with acute cerebral infarction:Preliminary findings [J].Eur Neurol,2021,38(1):38-42.
[4] 孔令宇,马文婷,杨亚勤,等.氯吡格雷联合瑞舒伐他汀对急性脑梗死患者血清炎性因子的影响[J].广东医学,2020,41(2):130-133.
[5] KORISH A A.Clopidogrel prophylaxis abates myocardial ischemic injury and inhibits the hyperlipidemia-inflammation loop in hypercholestrolemic mice[J].Arch Med Res,2020,51(6):515-523.
[6] 朱琳,田颖,沙红艳,等.回顾性分析氯吡格雷代谢型与脑梗死复发的相关性[J].中国老年学杂志,2022,42(13):3132-3135.
[7] WANG Z,LIU Z,WANG W,et al.Two common mutations within CYP2C19 affected platelet aggregation in Chinese patients undergoing PCI:A one-year follow-up study[J].Pharmacogenomics J,2019,19(2):157-163.
[8] ALMASSABI R F,MIR R,JAVID J,et al.Differential expression of serum proinflammatory cytokine TNF-α and genetic determinants of TNF-α,CYP2C19*17,miR-423 genes and their effect on coronary artery disease predisposition and progression[J].Life(Basel),2023,13(11):2142-2157.
[9] DUNVALD A D,JÄRVINEN E,MORTENSEN C,et al.Clinical and molecular perspectives on inflammation-mediated regulation of drug metabolism and transport[J].Clin Pharmacol Ther,2022,112(2):277-290.
[10] BERTRAND-THIBAULT C,BERRAHMOUNE H,THOMPSON A,et al.Genetic polymorphism of CYP2C19 gene in the stanislas cohort:A link with inflammation[J].Ann Hum Genet,2008,72(Pt 2):178-183.
[11] 吴雪婷,陈世春,吴志东,等.基于CYP2C19基因多态性探究氯吡格雷联合依达拉奉对急性脑梗死患者神经功能的影响[J].现代药物与临床,2022,37(4):750-754.
[12] 中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南2018[J].中华神经科杂志,2018,51(9):666-682.
[13] 陈光,付淼.急性缺血性脑卒中患者脑血管储备功能与其急诊治疗结局相关性分析[J].陕西医学杂志,2023,52(1):53-56.
[14] 张玲,郭利军.氢氯吡格雷与替格瑞洛在急性ST段抬高型心肌梗死合并2型糖尿病患者经皮冠状动脉介入治疗中的效果观察[J].陕西医学杂志,2020,49(10):1339-1342.
[15] 唐婉,林晓光.急性脑梗死患者血栓弹力图与CYP2C19基因多态性对氯吡格雷疗效评价的关系[J].心脑血管病防治,2022,22(3):55-57.
[16] 董婧,石国华,黄澍,等.CYP2C19、ABCB1和PON1基因多态性与氯吡格雷抑制血小板聚集作用的相关性研究[J].中国医院药学杂志,2018,38(23):2464-2468.
[17] 高乐,韩伟.CYP2C19基因多态性与临床因素对PCI术后氯吡格雷反应性的影响[J].中国实验诊断学,2023,27(1):68-72.
[18] LEE S H,JEONG Y H,HONG D,et al.Clinical impact of CYP2C19 genotype on clopidogrel-based antiplatelet therapy after percutaneous coronary intervention[J].JACC Cardiovasc Interv,2023,16(7):829-843.
[19] 蔡皓伟,高丽娜,周少旦,等.缺血性脑卒中患者CYP2C19基因多态性与氯吡格雷抗血小板作用的关系[J].山东医药,2015,55(28):49-50.
[20] 曹红元,王延江.急性脑梗死后炎性因子的动态变化及其与神经功能的相关性研究[C]//中华医学峰会暨中华医学会神经病学分会第八届全国中青年神经病学学术会议论文集.2015:243.
[21] 赵晶,钱进军.血清IL-11水平在急性脑梗死患者诊断和预后中的评估价值及其与血清脑源性神经营养因子的相关性[J].临床神经病学杂志,2024,37(1):32-36.
[22] AKASAKA T,HOKIMOTO S,SUETA D,et al.Sex differences in the impact of CYP2C19 polymorphisms and low-grade inflammation on coronary microvascular disorder[J].Am J Physiol Heart Circ Physiol,2016,310(11):h1494-h1500.
[23] 肖茹萍,姜礼双,崔亚,等.难治性胃食管反流病脾虚证CYP2C19基因表达及中药干预研究[J].中国中西医结合杂志,2018,38(1):25-28.
[24] AHMED M,KHAN S R,RAZZAQUE A,et al.Molecular analysis of CYP2C19 alleles and clopidogrel resistance among Bangladeshi patients with acute coronary syndrome[J].Cardiol Cardiovasc Med,2023,7(3):151-157.
[25] 杨森,吴上志,黄展航,等.CYP2C19基因多态性对肺部侵袭性真菌感染患儿伏立康唑血药谷浓度的影响及其潜在机制[J].解放军医学杂志,2023,48(10):1174-1179.
[26] DO SOCORRO S C P,WOYCINCK KOWALSKI T,ROSA FRAGA L,et al.NR3C1,ABCB1,TNF and CYP2C19 polymorphisms association with the response to the treatment of erythema nodosum leprosum[J].Pharmacogenomics,2019,20(7):503-516.

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备注/Memo

备注/Memo:
[基金项目]甘肃省自然科学基金资助项目(22JR5RA941)
更新日期/Last Update: 2025-04-07