氯吡格雷对兔动脉粥样硬化血清高敏C-反应蛋白和血管壁核因子-κB表达的影响

Effects of clopidogrel on serum hs-CRP and vascular wall NF-κB expression in atherosclerotic rabbits

目的:观察氯吡格雷对兔动脉粥样硬化(AS)血清高敏C-反应蛋白(hs-CRP)、血管壁核因子-κBp65mRNA(NF-κBp65mRNA)及p65蛋白表达的影响。方法:27只新西兰雄性白兔随机分为正常对照组(A组)、高胆固醇组(B组)和高胆固醇加氯吡格雷组(C组);分别用酶法、固相酶联免疫吸附试验(ELISA)、原位杂交法和组织形态学分析测定血脂、hs-CRP和血管壁p65含量、NF-κBp65mRNA表达及AS斑块/内膜面积比值及斑块最厚处内膜/中膜厚度比值。结果:B组和C组血脂、hs-CRP、血管壁NF-κBp65mRNA及p65表达均较A组显著升高(P<0.05);C组较B组血脂无明显差异而AS病变明显减轻(P<0.05),hs-CRP、血管壁NF-κBp65mRNA及p65蛋白表达均明显降低(P<0.05)。结论:氯吡格雷具有一定的抗AS作用,机制可能与抑制hs-CRP及NF-κB表达有关。

Objective To observe the effects of elopidogrel on the level of serum hypersensitivity C-responsive protein （hs-CRP） and the expressions of vascular wall nuclear factor-kappa Bp 65 mRNA （NF-κB p65 mRNA） and p65 subunit in atherosclerotic rabbits. Methods Twenty-seven New Zealand male rabbits were randomly assigned to the normal control group （group A）, high-cholesterol group （group B） and high-cholesterol plus clopidogrel group （group C）. Enzymatic assays, enzyme-linked immunosorbent assay, in situ hybridization and histomorphometry analysis were employed respectively to detect serum lipids, the levels of serum hs-CRP and atherosclerotic plaque p65 subunit, the expression of NF-κB p65 mRNA, and the atheroma/intima area ratio and the intima/media thickness ratio in the thickest portion of the plaque. Result The levels of serum lipid and hs-CRP and the expressions of vascular wall NF-κB p65 mRNA and p65 subunit in groups B and C were signifieandy elevated as compared with those in group A （P 〈 0.05）. There was no signilicant difference in serum lipids between group B and group C, while the severity of atherosclerosis, the level of serum hs-CRP and the expressions of vascular wall NF-κB p65 mRNA and p65 subunit were markedly decreased in group C （P 〈 0.05）. Conclusion Clopidogel plays a role in protection against atherosclerosis, which may be associated with inhibiting the expressions of hs-CRP and NF-κB.