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经皮冠状动脉介入治疗的急性冠状动脉综合征患者CYP2C19基因多态性分布及新加丹参饮对CYP2C19基因缺陷患者的干预作用
引用本文:陈骁康,王肖龙,王英杰,郭 蔚,陈铁军,沈智杰. 经皮冠状动脉介入治疗的急性冠状动脉综合征患者CYP2C19基因多态性分布及新加丹参饮对CYP2C19基因缺陷患者的干预作用[J]. 安徽中医药大学学报, 2016, 35(5): 15-20
作者姓名:陈骁康  王肖龙  王英杰  郭 蔚  陈铁军  沈智杰
作者单位:上海中医药大学附属曙光医院,上海,201203;上海中医药大学附属曙光医院,上海,201203;上海中医药大学附属曙光医院,上海,201203;上海中医药大学附属曙光医院,上海,201203;上海中医药大学附属曙光医院,上海,201203;上海中医药大学附属曙光医院,上海,201203
基金项目:国家自然科学基金项目(81573647,81403137);上海市科委“科技创新行动计划”(14401972202);上海市科委项目(13ZR1462100)
摘    要:目的 研究新加丹参饮对气滞血瘀型急性冠状动脉综合征经皮冠状动脉介入(acute coronary syndrome with percutaneous coronary intervention,ACS-PCI)患者的干预作用,并对CYP2C19基因缺陷患者进行亚组分析。方法 将92例气滞血瘀型ACS-PCI患者随机分为对照组和治疗组,对照组予常规西医治疗,治疗组在此基础上加用新加丹参饮进行治疗,2周后观察患者的肝肾功能、心肌酶谱、心绞痛疗效、中医临床症状及血小板聚集率等指标,来评价新加丹参饮的疗效。亚组研究:探讨CYP2C19基因多态性与氯吡格雷抵抗(clopidogrel resistance,CR)的相关性及新加丹参饮对CR患者的干预疗效。结果 治疗后治疗组心绞痛症状、中医症状改善情况明显优于对照组(P<0.05);治疗组纤维蛋白原、血小板聚集率改善作用优于对照组(P<0.05);CYP2C19*2基因型、CYP2C19*3基因型均与CR具有显著相关性(P<0.05);CYP2C19*2突变纯合子合并CYP2C19*3突变杂合子发生CR概率(4/4)最高,随着突变链增多,CR发生率有一定上升趋势;治疗组在降低CR患者血清纤维蛋白原方面优于对照组(P<0.05),在降低CR患者血小板聚集率方面与对照组相当(P>0.05)。结论 新加丹参饮干预治疗能有效改善患者心绞痛症状、中医临床症状;CYP2C19基因多态性与CR的发生密切相关;新加丹参饮对CR患者的纤维蛋白原、血小板聚集率具有改善作用。

关 键 词:CYP2C19  基因多态性  新加丹参饮  氯吡格雷抵抗  血小板聚集率  纤维蛋白原

CYP2C19 Gene Polymorphism Distribution in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention and Efficacy of Xinjia Danshen Decoction in Patients with CYP2C19 Gene Deficiency
Affiliation:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Abstract:Objective To investigate the efficacy of Xinjia Danshen Decoction in patients with qi-stagnation and blood-stasis type acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), and to perform a subgroup analysis of patients with CYP2C19 gene deficiency. Methods A total of 92 patients with qi-stagnation and blood-stasis type ACS who underwent PCI were randomly divided into control group and treatment group. The patients in the control group were given conventional Western medicine treatment, and those in the treatment group were given Xinjia Danshen Decoction in addition to the conventional Western medicine treatment. The indices including liver and renal function parameters, myocardial zymogram, angina pectoris treatment outcome, traditional Chinese medicine (TCM) clinical symptoms, and platelet aggregation rate were observed after 2 weeks to evaluate the clinical effect of Xinjia Danshen Decoction. A subgroup analysis was performed to investigate the association between CYP2C19 gene polymorphisms and clopidogrel resistance and the efficacy of Xinjia Danshen Decoction in patients with clopidogrel resistance. Results After treatment, the treatment group had significantly better improvements in angina pectoris symptoms, TCM symptoms, fibrinogen, and platelet aggregation rate compared with the control group (all P<0.05). The CYP2C19*2 and CYP2C19*3 genotypes were significantly associated with clopidogrel resistance (P<0.05). The patients with CYP2C19*2 mutation homozygote and CYP2C19*3 mutation heterozygote had the highest probability of clopidogrel resistance (4/4), and with the increasing number of mutation chains, the incidence rate of clopidogrel resistance tended to increase. The patients with clopidogrel resistance in the treatment group had a significantly better outcome in the reduction of serum fibrinogen compared with those in the control group (P<0.05), and there was no significant difference in the reduction of platelet aggregation rate in patients with clopidogrel resistance between the two groups (P>0.05). Conclusion Xinjia Danshen Decoction can effectively improve angina pectoris symptoms and TCM symptoms. CYP2C19 gene polymorphisms are closely associated with the development of clopidogrel resistance. Xinjia Danshen Decoction can improve fibrinogen and platelet aggregation rate in patients with clopidogrel resistance.
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