Abstract：Objective To explore the relationship between gene polymorphism of cytochrome P450 2C19(CYP2C19) and curative effect of butyphthalide in acute cerebral infarction (ACI). Methods A total of 216 patients with ACI were enrolled as the research objects between February and December 2023. All patients were treated with butyphthalide, and blood concentration of butyphthalide was detected after 7d of treatment. According to scores of National Institutes of Health Stroke Scale (NHISS), patients were divided into effective group (NHISS score decreased by ≥45%, n=112) and ineffective group (NHISS score decreased by <45%, n=104). CYP2C19 gene polymorphisms were detected by high-throughput genotyping technique. The effects of CYP2C19 gene polymorphisms on curative effect of butyphthalide in ACI patients were analyzed by multivariate Logistic regression analysis. Results After 7d of treatment, scores of NIHSS and mRS were decreased, and ADL score was increased. After 7d of treatment, blood concentration of fast-metabolism butyphthalide was higher than that in intermediate-metabolism and slow-metabolism butyphthalide. The frequencies of GG gene at CYP2C19*2 and CYP2C19*3 loci in effective group were higher than those in ineffective group. Binary Logistic regression analysis showed that atrial fibrillation (OR=2.366, P=0.019), NIHSS score before treatment (OR=2.358, P=0.016), CYP2C19*2(OR=4.423, P<0.001) and CYP2C19*3(OR=2.316, P=0.028) were all independent risk factors affecting the curative effect of butyphthalide in ACI patients. Conclusion The polymorphisms of CYP2C19 gene are related to the curative effect of butyphthalide in ACI, and curative effect is worse in patients with A allele.
[1] FEIGIN V L, STARK B A, JOHNSON C O, et al.Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019[J]. The Lancet Neurology, 2021, 20(10): 795-820. [2] 杜志刚, 伊红丽, 王宇, 等. 丁苯酞联合阿替普酶治疗缺血性脑血管病的疗效及其对颈动脉粥样硬化程度和血清脂质过氧化物, 血栓前体蛋白水平的影响[J]. 临床内科杂志, 2023, 40(2): 129-130. [3] 朱存良, 易芳芳, 谭若利, 等. 替罗非班与丁苯酞联合治疗对发病24 h内未行溶取栓治疗的急性缺血性脑卒中的疗效影响[J]. 临床和实验医学杂志, 2023, 22(3): 254-257. [4] LV J, ZHAO D, ZHAO G, et al.Efficacy and safety of butylphthalide in secondary prevention of stroke: study protocol for a multicenter, real world trial based on Internet[J]. BMC neurology, 2022, 22(1): 1-11. [5] 李吉, 厉伟兰, 牛一民, 等. 基于血浆代谢组学评价不同神经保护剂联用方案对缺血性脑卒中生物标志物的影响[J]. 中国医院药学杂志, 2021, 41(14): 1438-1445. [6] YUAN X, YUAN S, WU G, et al.Genetic polymorphism of clopidogrel metabolism related gene CYP2C19 gene in Chinese from Foshan area of Guangdong Province[J]. Hematology, 2022, 27(1): 1056-1061. [7] ELTALAL S, EL AYOUTY M, EL-SAID A, et al.CYP2C9(*2&*3) and CYP2C19(*2&*3) polymorphisms among children with nonlesional epilepsy: a single-center study[J]. Acta Neurol Belg, 2021, 121(6): 1623-1631. [8] 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. [9] LYDEN P D, LU M, LEVINE S R, et al.A modified national institutes of health stroke scale for use in stroke clinical trials: preliminary reliability and validity[J]. Stroke, 2001, 32(6): 1310-1317. [10] 巫嘉陵, 安中平, 王世民, 等. 脑卒中患者日常生活活动能力量表的信度与效度研究[J]. 中国现代神经疾病杂志, 2009, 9(5): 464-468. [11] 孙冲, 徐迪荣, 李碧磊. 改良Rankin量表在急性大面积脑梗死长期生存的预后价值[J]. 医学研究杂志, 2012, 41(12): 179-182. [12] The Neurological Society of Chinese Medical Association. Group of Cerebrovascular Disease of the Neurological Society of Chinese Medical Association. The Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke in China (2014)[J]. Chin J Neurol, 2015, 48(4): 246-257. [13] ZHANG S, ZHU J, LI H, et al.Associations of CYP2C19 and F2R genetic polymorphisms with platelet reactivity in Chinese ischemic stroke patients receiving clopidogrel therapy[J]. Pharmacogenet Genomics, 2022, 32(4): 138-143. [14] YAN Y, HAO R, ZHAO X, et al.Relationship between CYP2C19* 2, * 3 gene polymorphism and the recurrence in ischemic stroke patients treated with clopidogrel in China: A meta-analysis[J]. J Stroke Cerebrovasc Dis, 2022, 31(11): 106798. [15] 刘天芳, 李红, 杨晓莉. 丁苯酞联合重组组织型纤溶酶原激活剂静脉溶栓治疗急性缺血性脑卒中临床疗效观察[J]. 实用医院临床杂志, 2023, 20(5): 98-101. [16] BU X, XIA W, WANG X, et al.Butylphthalide inhibits nerve cell apoptosis in cerebral infarction rats via the JNK/p38 MAPK signaling pathway[J]. Exp Ther Med, 2021, 21(6): 1-6. [17] LI L, LUO S.Analysis of CYP2C19 Gene Genotype in Patients with Acute Cerebral Infarction and Its Relationship with Disease Progression[J]. Russian Journal of Genetics, 2023, 59(10): 1092-1097. [18] 朱晓茹, 陈国芳, 姚美雪, 等. 即时检测CYP2C19基因型精准指导下高危非致残性缺血性脑血管事件的抗血小板治疗[J]. 中华神经科杂志, 2023, 56(4): 365-373. [19] 冯晋, 孙航, 杨琼英, 等. 活性氧介导血脑屏障损伤在缺血性脑卒中的作用机制[J]. 医学综述, 2022, 28(17): 3329-3334. [20] 万俊, 白艳杰, 王岩, 等. 长链非编码RNA与缺血性脑卒中后的神经免疫炎症及相关信号通路[J]. 中国组织工程研究, 2024, 28(20): 3265-3271. [21] 李龙, 栾家杰, 金莞, 等. CYP2C19基因多态性对PCI术后氯吡格雷药动学及药效学影响的临床评价[J]. 中国医院药学杂志, 2023, 43(4): 383-388. [22] 蔡智立, 何奕涛, 周致帆, 等. 脑梗死超早期静脉溶栓治疗的疗效及相关因素分析[J]. 中国实用神经疾病杂志, 2020, 23(5): 380-385.
2024, Vol. 21 
