抗凋亡多肽Gly14-Humanin对动脉粥样硬化模型小鼠血小板高敏感性以及脂质斑块形成的作用  

Effect of Anti-apoptotic Factor~[Gly14]-Humanin on Platelet Hypersensitivity and Lipid Plaque Formation in the LDLR-deficient Mice

作　　者：胡淑鸿 杨飞[1] 曹宜人 任丽洁[1] 

机构地区：[1]苏州大学唐仲英血液学研究中心,江苏省苏州市215123

出　　处：《中国动脉硬化杂志》2015年第8期789-794,共6页Chinese Journal of Arteriosclerosis

摘　　要：目的抗凋亡多肽Humanin可以延缓动脉粥样硬化脂质斑块形成,其机制可能是抑制氧化型低密度脂蛋白诱导的氧化性应激和内皮细胞凋亡,但Humanin对动脉粥样硬化状态下血小板高敏感性的影响尚无报道。本研究评价了Humanin衍生物([Gly14]-Humanin,HNG)对低密度脂蛋白受体(LDLR)敲除小鼠动脉粥样硬化形成以及血小板高敏感性的影响。方法将8周龄雄性野生型(wild type,WT)和低密度脂蛋白受体敲除小鼠进行实验分组,包括对照组(WT小鼠喂食普通饲料,CD组)、模型组(LDLR-/-小鼠喂食高脂饲料,HFD组)、实验组(LDLR-/-小鼠喂食高脂饲料的同时注射HNG,HFD+HNG组)。分别于4周、12周、24周,进行下腔静脉取血,分离洗涤血小板,进行血小板聚集实验并分离血清进行血脂含量的测量。适时分离主动脉进行苏丹IV染色,观察主动脉内表面粥样脂质斑块形成,利用Image-Pro Plus图像处理软件分析斑块面积大小。结果与对照组相比,喂食高脂饲料24周后,模型组小鼠主动脉内有大量粥样斑块形成,并且随着喂食高脂时间的延长,具有明显的脂蛋白水平的变化。模型组小鼠血小板在二磷酸腺苷(adenosine diphosphate,ADP)诱导下的聚集作用显著增强(P<0.01),更重要的是,HFD+HNG组小鼠的斑块面积明显减小(P<0.01),且血小板对ADP所诱导的血小板聚集明显低于HFD组(P<0.01)。结论 HNG抑制动脉粥样硬化模型小鼠血小板高敏感性,可能是减缓动脉粥样硬化脂质斑块形成的机制之一。Aim Anti-apoptotic factor Humanin may have a protective effect on endothelial function and progression of atherosclerosis by modulating oxidative stress and apoptosis in the developing plaque. But there has been no report on whether it has an impact on platelet hypersensitivity in the atherosclerotic mouse models. Here we examined the effect of Humanin analogue（[Gly14]-Huamnin,HNG） on the development of atherosclerosis and platelet hypersensitivity in lowdensity lipoprotein receptor knock-out mice. Methods Mice（ 8 weeks old） were grouped into wild type mice on normal chow diet（ CD） and LDLR- /-mice on high fat diet（ HFD） with or without HNG injection. At week 4,12,24,blood was obtained from the inferior vena cava and platelets were isolated and measured for aggregation in a Chrono-log lumi-aggregometer and serum lipid level was measured. At the right time,the aorta was stained with Sudan IV and lipid deposition was quantified using Image-Pro Plus. Results After 24 weeks on HFD,LDLR^- /-mice showed large area of plaques formed in the aorta and an altered lipid profile as compared to WT mice on CD. Platelets of LDLR^- /-mice on HFD showed significantly higher reactivity than WT mice on CD in response to ADP（ n = 10,P〈0. 01）. Most importantly,administration of HNG inhibited the formation of atherosclerotic plaque in the aorta（ n = 10,P〈0. 01） and decreased platelet reactivity to ADP（ n = 10,P〈0. 01） in LDLR^- /-mice on HFD. Conclusion Our data showed that HNG reduces platelet hypersensitivity in the setting of hyperlipidemia,providing a potential alternative mechanism by which HNG reduces plaque formation.

关 键 词：低密度脂蛋白受体 动脉粥样硬化 脂质斑块 血小板 

分 类 号：R363[医药卫生—病理学]