目的 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。方法 通过真实世界研究,于2019年1月-2020年7月在东莞市人民医院收集氯吡格雷联合依达拉奉注射液治疗的急性脑梗死患者。采用实时荧光定量PCR法检测患者的CYP2C19基因型,根据基因型将患者分为快代谢型组、中间代谢型组和慢代谢型组。通过神经功能损伤评分量表(NIHSS)评价患者急性脑梗死的神经功能。结果 270例急性脑梗死患者中快代谢型(CYP2C19*1/*1)患者102例,占37.78%;中间代谢型(CYP2C19*1/*2、CYP2C19*1/*3、CYP2C19*2/*17、CYP2C19*3/*17)患者140例,占51.85%;慢代谢型(CYP2C19*2/*2、CYP2C19*3/*3、CYP2C19*2/*3)患者28例,占10.37%。快代谢型、中间代谢型患者治疗后的NIHSS评分显著降低,差异有统计学意义(P<0.05)。慢代谢型没有统计学意义。进一步分析发现,与慢代谢型患者相比,快代谢型、中间代谢型患者治疗前后的NIHSS评分显著下降,差值有统计学意义(P<0.05)。结论 CYP2C19基因多态性在氯吡格雷联合依达拉奉治疗急性脑梗死患者的神经功能影响具有差异。快代谢型和中间代谢型患者神经功能显著改善,慢代谢型患者没有显著性差异,建议结合临床情况,及时调整治疗方案。

Objective To explore the neurological function of CYP2C19 gene polymorphism in clopidogrel combined with edaravone in treatment of patients with acute cerebral infarction.Methods Patients with acute cerebral infarction in Dongguan People's Hospital treated with clopidogrel combined with edaravone were collected from January 2019 to July 2020 in a real-world study. The CYP2C19 genotype of the patients was detected by Real-time Fluorescence Quantitative PCR, and the patients were divided into extensive metabolizers group, intermediate metabolizer group, and poor metabolizer group according to the genotype. The neurological function of acute cerebral infarction was evaluated by National Institutes of Health Stroke Scale (NIHSS).Results A total of 270 patients with acute cerebral infarction treated with clopidogrel combined with edaravone injection were collected, of which 102 patients with extensive metabolizers group (CYP2C19*1/*1) accounted for 37.78%. There were 140 patients with intermediate metabolizer group (CYP2C19*1/*2, CYP2C19*1/*3, CYP2C19*2/*17, and CYP2C19*3/*17), accounting for 51.85%. There were 28 patients with poor metabolizer group (CYP2C19*2/*2, CYP2C19*3/*3, and CYP2C19*2/*3), accounting for 10.37%. The NIHSS scores of patients in extensive metabolizers and intermediate metabolizer treated with clopidogrel combined with edaravone were significantly decreased, and the difference were statistically significant (P < 0.05). Poor metabolizer group was not statistically significant. Compared with patients in poor metabolizer group, NIHSS scores of patients in extensive metabolizers and intermediate metabolizer group were decreased, with statistical significance (P < 0.05).Conclusion The effect of CYP2C19 gene polymorphisms on neurological function in patients with acute cerebral infarction treated with clopidogrel combined with edaravone is different. The neurological function of patients with extensive metabolizers and intermediate metabolizer were significantly decreased, and there was no significant difference in patients with poor metabolizer group. It is recommended to adjust the treatment plan in time according to the clinical situation.

R971

广东省医学科学技术研究基金项目(B2020086);广东省医院药学研究基金(澳美基金)资助项目(2021A08)