冠心康对载脂蛋白E基因敲除小鼠主动脉粥样斑块及CD40L表达的影响

Effects of Guanxinkang on Atheromatous Plaque and CD40L Expression in Atherosclerosis of Apolipoprotein E-deficient Mice

目的:通过观察中药复方冠心康对载脂蛋白E基因敲除(ApoE-/-)小鼠主动脉粥样硬化斑块病理形态及CD40L表达的影响,探讨冠心康抗动脉粥样硬化的作用机制。方法:45只8周龄雄性ApoE-/-小鼠予高脂饲料喂养建立实验性动脉粥样硬化小鼠模型,至第12周龄时,ApoE-/-小鼠随机分为模型对照组、氯吡格雷组和冠心康组。取15只8周龄近交系C57BL/6小鼠作为正常对照组给予普通饲料喂养。各组于第24周取材检测血脂、血浆sVCAM-1和sICAM-1及CD40L含量、检测外周血血小板表面CD40L表达;观察主动脉组织病理形态学改变;检测主动脉组织CD40L表达强度。结果:冠心康组和氯吡格雷组的血浆sVCAM-1和sICAM-1的浓度,血浆CD40L、血小板表面CD40L和动脉组织CD40L的表达明显降低,与模型组比较有显著差异(P<0.01),冠心康组和氯吡格雷组相比无显著性差异(P>0.05)。此外冠心康组血脂水平明显降低,与模型组比较有显著差异(P<0.01);氯吡格雷组与模型对照组之间的血脂水平比较无统计学意义(P>0.05)。此外冠心康减轻AS病变程度方面均优于氯吡格雷组,两组与模型组对比明显减轻。结论:冠心康和氯吡格雷都可通过抑制血小板活化,减少CD40L和黏附分子表达,减轻炎症反应,抑制AS病变,起到抗动脉粥样硬化的作用,揭示冠心康抗动脉粥样硬化的作用机制与下调CD40-CD40L系统,抑制血小板活化,降低CD40L表达有关。

Objective ：To observe the effects of Guanxinkang on the pathological morphology of atheromatous plaque and the expression of CIMOL of ApoE - deficient mice with atherosclerosis, and to explore the mechanisms of Guanxinkang antiatherosclerotic action. Methods ： Fifty 8 - week - old male ApoE -/- mice were fed high fat diet to establish experimental mouse model of atherosclerosis. 12 weeks old ApoE-imice were randomly divided into model group, clopidogrel group and Guanxinkang group. Fifteen 8 - week - old inbred C57BIM6 mice that were given normal diet were used as normal control group. Each group in the first 24 weeks derived serum lipids, plasma sVCAM - 1 and sICAM - 1 and CIMOL levels,peripheral blood platelet surface CD40L expression. We observed pathological changes aorta and detected the aortic tissue CI）40L expression intensity. Results ： Plasma sVCAM - 1 and sICAM - 1 concentrations, plasma CD40L, platelet surface CIMOL and CIMOL expression in arterial tissue of Guanxinkang group and clopidogrel group were significantly decreased and compared with the model group there was significant difference （ P 〈 0.01 ）. Guanxinkang group and clopidogrel group had no significant difference （P 〉 0.05）. Furthermore, Guanxinkang group＇ s blood lipid levels were significantly lower and compared with the model group there was significant difference （P 〈 0.01 ）. Clopidogrel group and model control lipid levels between the groups were not statistically significant （ P 〉 0.05 ）. Furthermore, Guanxinkang group on mitigating AS severity was better than clopidogrel group. Two groups significantly reduced compared with the model group. Conclusion ： Both Guanxinkang and clopidogrel play an anti - atherosclerotic effect by inhibiting platelet activation, reducing the expression of CD40L and adhesion molecules, reducing inflammation, inhibiting AS lesions, revealing the mechanism of Guanxinkang antiatherugenic with reducing CD40 - CIMOL system,inhibiting platelet activation and reducing the expression of CD40L relevant.