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

发布时间：2018-02-11 19:33

本文关键词： 低密度脂蛋白受体动脉粥样硬化脂质斑块血小板　出处：《中国动脉硬化杂志》2015年08期 　论文类型：期刊论文

【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(P0.01),更重要的是,HFD+HNG组小鼠的斑块面积明显减小(P0.01),且血小板对ADP所诱导的血小板聚集明显低于HFD组(P0.01)。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。
[Abstract]:Objective Anti-apoptotic polypeptide Humanin can delay the formation of atherosclerotic lipid plaques by inhibiting oxidative stress induced by oxidized low density lipoprotein (LDL) and endothelial cell apoptosis. However, the effect of Humanin on platelet hypersensitivity in atherosclerosis has not been reported. In this study, we evaluated the role of [Gly14] -human inhg in atherosclerosis formation and platelet hypersensitivity in low density lipoprotein receptor (LDLR) knockout mice. Methods eight week-old male wild type wild type WTs and low density lipoprotein receptor knockout mice were divided into two groups. The control group was fed with normal diet (CD group), the model group (LDLR-r-mice) was fed with high fat diet (HFD) group, the experimental group (LDLR-r-mice) was fed with high fat diet and the control group was injected with HNGLR-HFD HNG at the same time. Blood was collected from the inferior vena cava (IVC) at 4 weeks and 12 weeks to 24 weeks, respectively. The platelet was separated and washed, the platelet aggregation test was carried out and the serum was separated to measure the blood lipid content. The aorta was separated for Sudan IV staining in time to observe the formation of atherosclerotic plaque on the inner surface of aorta. Image-Pro Plus image processing software was used to analyze the size of plaque. Results compared with the control group, there were a large number of atherosclerotic plaques in the aorta of the model group after 24 weeks of high fat diet. The platelet aggregation induced by adenosine diphosphate in model group significantly increased P0.01a, and more importantly, the plaque area of mice in HNG group significantly decreased P0.01a, and the platelet effect on ADP sites was also significantly increased in the model group. The platelet was induced by adenosine diphosphate in the model group, and the platelet aggregation was induced by adenosine diphosphate in the model group, and more importantly, the plaque area of the mice in the HNG group was significantly reduced. The platelet aggregation induced by HNG was significantly lower than that in HFD group (P 0.01). Conclusion HNG has high platelet sensitivity in atherosclerotic mice. It may be one of the mechanisms that slow down the formation of atherosclerotic lipid plaque.
【作者单位】：苏州大学唐仲英血液学研究中心;
【分类号】：R543.5;R-332

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