氯吡格雷对基于CYP2C19分型的健康人血浆eNOS和NO水平影响的研究（英文）

Research on the role of clopidogrel in improving endothelial nitric oxide synthase(eNOS) along with decreasing nitric oxide(NO) in Chinese healthy subjects independently of CYP2C19 genotype

目的:临床研究显示氯吡格雷可以改善不同CYP2C19基因型健康受试者以及冠心病患者的血管内皮功能,故本研究探讨氯吡格雷的内皮功能保护机制。方法:6名基因型为CYP2C19*1/*1和6名基因型为CYP2C19*2/*2 or*2/*3的健康受试者纳入本实验。所有健康受试者均于空腹12 h后单次服用负荷剂量氯吡格雷300 mg。服药前(0 h)及服药后4 h、24 h静脉采血,检测受试者血浆e NOS、NO、ADMA浓度和血清hs CRP浓度。结果:口服负荷剂量氯吡格雷300 mg 4 h及24 h后,CYP2C19*1/*1组及CYP2C19*2/*2 or*2/*3组血浆e NOS浓度均显著上升,且两组间e NOS浓度差异无统计学意义。同时,CYP2C19*1/*1和CYP2C19*2/*2 or*2/*3组血浆NO水平在口服氯吡格雷4 h、24 h后均显著降低,且两组间NO水平差异无统计学意义。氯吡格雷对两组CYP2C19基因健康受试者血浆(清)ADMA、hs CRP浓度无显著影响。结论:本研究首次证实单负荷剂量氯吡格雷(300 mg)提高中国健康受试者血浆e NOS浓度并伴随血浆NO水平降低,包括基因型是CYP2C19*1/*1和CYP2C19*2/*2 or*2/*3。

AIM：Clopidogrel has been demon- strated to improve endothelial function in healthy subjects with different CYP2C19 genotypes and in patients with coronary artery disease （CAD）. Its en- dothelial protective mechanism has studied in this research. METHODS：Six healthy participants with CYP2C19＊ 1/＊1 and six healthy participants with CYP2C19 ＊ 2/＊ 2 or＊ 2/＊ 3 were enrolled. All par- ticipants took 300 mg of clopidogrel orally after 12 hours of fasting. Laboratory indexes including endo- thelial NOS （eNOS）, nitric oxide （NO）, asymmet- ric dimethylarginine （ADMA）, and high sensitivity C reactive protein （hsCRP） were determined at 0, 4 h and 24 h after oral administration of 300 mg of clo- pidogrel. RESULTS： Plasma eNOS levels were increased significantly at 4h and 24h after a loading- dose administration of clopidogrel in both CYP2C19＊ 1/＊ 1 and CYP2C19＊ 2/＊ 2 or＊ 2/＊ 3 groups, and no significant difference was shown be- tween the two groups. Meanwhile plasma NO concen- trations were decreased significantly at 4h and 24 h after the administration of clopidogrel in both CYP2C19＊ 1/＊ 1 and CYP2C19＊ 2/＊ 2 or＊ 2/＊ 3 groups, and no great difference was shown between the two groups. ADMA and hsCRP levels were not affected by clopidogrel in healthy participants with different CYP2C19 genotype. CONCLUSION ： This study for the first time demonstrates that administra- tion of a loading-dose of clopidogrel （300 mg） im- proves plasma eNOS levels along with decreases plasma NO level in healthy Chinese subjects no mat- ter with CYP2C19 ＊ 1/＊ 1 or with CYP2C19＊ 2/＊ 2 or ＊ 2/＊ 3 genotype.