阿司匹林对波动高糖诱导内皮损伤过程中血小板活化的影响

摘要

Aim To investigate the influence of aspirin on platelet activation during vascular endothelial injury induced by high blood glucose fluctuations .Methods In this study , "fluctuant high blood glucose cultured human umbilical vein endothelial cell ( HUVEC ) mod-el" and "human platelet-HUVEC supernate experi-mental system" were established in vitro, as well as type 2 diabetes mellitus ( T2DM) rat model with high blood glucose fluctuation in vivo. There were four groups: normal glucose ( N ) , steady high glucose (W), fluctuant high glucose ( B), and aspirin group ( ASA) .At the end of the study , the peripheral blood platelet maximum aggregation rate , levels of sE-selec-tin, von Willebrand factor ( vWF ) and platelet mem-brane protein level of CD62p were determined.Results In comparison with N group, levels of sE-selectin,vWF, the platelet maximum aggregation rate and plate-let membrane protein level of CD 62 p in W group and B group all significantly increased ( P <0.01 ) , mean-while B group significantly increased further compared with W group ( P <0.05 or P <0.01 ) .Pretreatment with ASA significantly decreased the elevated levels of sE-selectin, vWF, the platelet maximum aggregation rate and CD62p induced by high glucose fluctuations (P<0.01).Conclusions High blood glucose fluctu-ations can not only aggravate endothelial injury , but al-so promote platelet aggregation obviously , while aspirin has obvious antagonistic effects on these effects .%目的 观察阿司匹林对波动高糖诱导内皮损伤过程中血小板活化的影响.方法 体外构建波动高糖损伤人脐静脉内皮细胞模型,并以模型组细胞上清液作为诱导剂,与健康人血小板进行共孵育;体内构建2型糖尿病血糖波动大鼠模型.体内、外实验均分为正常(N)组、稳定高糖(W)组、波动高糖(B)组和波动高糖+阿司匹林(ASA)组.分别应用细胞计数试剂盒测得阿司匹林半数致死量,按实验动物与人体表面积比等效剂量换算表计算阿司匹林体外、体内实验中的剂量.细胞实验中给予ASA(1 mmol·L-1)干预15 min后加入健康人血小板,测定人血小板最大聚集率、细胞培养上清液sE-selectin和vWF水平;动物实验中给予ASA(60 mg·kg-1·d-1)灌胃1次,干预6周后测定大鼠血清sE-selec-tin和vWF水平,以及大鼠血小板膜蛋白CD62p表达.结果与N组相比,W组和B组细胞上清及2型糖尿病大鼠血清vWF和sE-selectin含量均明显增多(P<0.01),健康人外周血血小板最大聚集率及大鼠血小板膜蛋白CD62 p表达均明显增加(P<0.01),且两组间具有明显差异(P<0.05或P<0.01).ASA干预后,vWF和sE-selectin含量均明显下降(P<0.01),人血小板最大聚集率及大鼠血小板膜蛋白CD62p表达亦明显降低(P<0.01).结论 波动高糖不仅可以导致明显的血管内皮损伤,也可诱发血小板出现过度活化聚集,阿司匹林对此均具有明显抑制效应.