不同剂量氯吡格雷对冠状动脉粥样硬化性心脏病患者凝血功能及炎症反应的影响

Effects of different doses of clopidogrel on coagulation function and inflammatory response in patients with coronary atherosclerosis heart disease

目的探讨不同剂量氯吡格雷对冠状动脉粥样硬化性心脏病患者血小板膜糖蛋白、血小板聚集率及抑制率、凝血功能及炎症因子的影响。方法选择2014年1月至2017年10月于淮安市第二人民医院就诊的96例CAHD患者为研究对象,将患者分为高剂量组(n=50)和常规剂量组(n=46)。2组患者均给予阿司匹林及调脂药物等常规对症治疗措施,在此基础上,常规剂量组患者口服氯吡格雷,首剂300 mg,随后每次75 mg维持治疗,每日1次,治疗7 d;高剂量组患者首剂口服氯吡格雷600 mg,随后每次150 mg维持治疗,每日1次,治疗7 d。采用酶联免疫吸附法测定2组患者治疗前及治疗7 d后血浆血小板活化分子α颗粒膜蛋白(CD62p)、可溶性白细胞分化抗原40配体(s CD40L)水平和血清单核细胞趋化因子-1(MCP-1)水平;流式细胞计数仪检测2组患者治疗前及治疗7 d后血浆溶酶体膜蛋白(CD61)、溶酶体完整膜蛋白(CD63);使用全自动血凝分析仪检测2组患者治疗前及治疗7 d后血浆纤维蛋白原(FIB)水平、活化部分凝血酶原时间(APTT)、凝血酶时间(TT)、凝血酶原时间(PT);采用血小板聚集仪检测2组患者治疗前及用药24 h后血小板聚集率和血小板抑制率;免疫散射比浊法检测2组患者治疗前和治疗7 d后血清高敏C反应蛋白(hs-CRP)水平。结果治疗前2组患者血小板膜糖蛋白CD61、CD63比率及血浆CD62p、s CD40L水平、血小板聚集率、血小板抑制率、FIB、APTT、PT、TT、血清MCP-1和hs-CRP水平比较差异均无统计学意义(P>0.05)。2组患者治疗7 d后CD61、CD63比率及血浆CD62p、FIB水平、血清MCP-1、hs-CRP水平均显著低于治疗前(P<0.05);2组患者治疗7 d后血浆s CD40L水平及APTT、PT、TT与治疗前比较差异均无统计学意义(P>0.05)。治疗7 d后,高剂量组患者CD61、CD63比率及血浆CD62p、FIB水平和血清MCP-1、hs-CRP水平均显著低于常规剂量组(P<0.05);2组患者血浆s CD40L水平比较差异无统计学意义(P>0.05)。2组患者服药后24 h血小板聚集率均显著低于治疗前,血小板抑制率均显著高于治疗前(P<0.05);服药后24 h,高剂量组患者血小板聚集率显著低于常规剂量组,血小板抑制率显著高于常规剂量组(P<0.05)。高剂量组和常规剂量组患者不良反应发生率分别为6.00%(3/50)、2.17%(1/46),2组患者不良反应发生率比较差异无统计学意义(χ^2=0.880,P>0.05)。结论高剂量氯吡格雷可有效降低血小板膜糖蛋白及炎症反应,降低机体对氯吡格雷的抵抗,明显改善患者凝血功能。

Objective To investigate the effects of different doses of clopidogrel loads on platelet membrane glycoprotein,platelet aggregation rate and inhibition rate,coagulation function and inflammatory factors in patients with coronary atherosclerosis heart disease(CAHD).Methods Ninty-six CAHD patients in the Second People’s Hospital of Huaian from January2014 to October 2017 were selected as the study objects.The patients were divided into high dose group(n=50)and conventional dose group(n=46).All patients were given aspirin,lipid-regulating drugs and other conventional symptomatic treatment measures.Based on this,the patients in the conventional dose group took the clopidogrel orally,the first dose was 300 mg per day,followed by 75 mg per day maintenance treatment,once a day for 7 days;the patients in the high-dose group took orally clopidogrel 600 mg for the first dose,followed by 150 mg maintenance treatment,once a day for 7 days.The levels of platelet membrane glycoprotein ofαgrana membrane protein(CD62p),soluble CD40 ligand(sCD40L)and serum monocyte chemokine-1(MCP-1)of patients in the two groups were measured by enzyme-linked immunosorbent assay before and 7 days after treatment;the plasma lysosomal membrane protein(CD61),lysosomal integral membrane protein(CD63)of patients in the two groups were measured by flow cytometer before and 7 days after treatment;the plasma fibrinogen(FIB),activated partial prothrombin time(APTT),prothrombin time(PT)and blood enzyme(TT)of patients in the two groups were measured by the automatic hemagglutination analyzer before and 7 days after treatment;the platelet aggregation rate,platelet inhibition rate of patients in the two groups were measured by the platelet aggregation instruments before and 24 hours after taking medicine;the serum high-sensitivity C-reactive protein(hs-CRP)level of patients in the two groups were measured by the immune scattering turbidimetry.Results There was no significant difference in the platelet membrane glycoprotein CD61,CD63 ratio,the levels of plasma CD62p and s CD40L,platelet aggregation rate,platelet inhibition rate,FIB,APTT,PT,TT,serum levels of MCP-1 and hs-CRP between the two groups before treatments(P>0.05).The CD61 and CD63 ratio,the levels of plasma CD62p and FIB,the serum levels of MCP-1,hs-CRP of patients in the two groups at 7 d after treatment were significantly lower than those before treatment(P<0.05);there was no significantly difference in the plasma level of s CD40L and APTT,PT,TT before treatment and 7 d after treatment in the two groups(P>0.05).After 7 days of treatment,the CD61 and CD63 ratio,the levels of plasma CD62p and FIB,the serum levels of MCP-1,hs-CRP of patients in high dose group were significantly lower than those in the conventional dose group(P<0.05);there was no significantly difference in the plasma level of s CD40L between the two groups(P>0.05).Compared with before treatment,the platelet inhibition rate of patients in the two groups was decreased,and the platelet aggregation rate of patients in the two groups was increased at 24 hours after taking medicine(P<0.05);At 24 hours after taking medicine,the platelet inhibition rate of patients in the high dose group was higher than that in the conventional dose group(P<0.05),the platelet aggregation rate of patients in the high dose group was lower than that in the conventional dose group(P<0.05).The incidence of adverse reaction of patients was 6.00%(3/50),2.17%(1/46);there was no statistic difference in the incidence of adverse reaction between the two groups(χ^2=0.880,P>0.05)Conclusion High dose clopidogrel can effectively reduce the platelet membrane glycoprotein and inflammatory response,reduce the resistance of the body to clopidogrel,and significantly improve the coagulation function of patients.