李华,李鸿雁,金圣宇
LI Hua,LI Hongyan,JIN Shengyu

• 1:延边大学附属医院体检科
• 2:延边大学附属医院血液内科

摘要(Abstract)：

目的:观察血管性血友病因子裂解酶(ADAMTS13)对动脉粥样硬化小鼠模型的影响及机制。方法:分别以高脂肪西方饮食喂养6周龄的野生型小鼠(WT)、载脂蛋白E缺陷(Apo E~(-/-))和ADAMTS13缺陷小鼠(Adamts13~(-/-))及ADAMTS13基因敲除的载脂蛋白E缺乏(Adamts13~(-/-)Apo E~(-/-))小鼠12周,处死小鼠分离主动脉,用油红O染色后采用NIH Image J软件量化分析动脉硬化程度;采用Western blot分析小鼠血浆中血管性血友病因子(VWF)多聚体的分布,同时检测总胆固醇、高密度脂蛋白和甘油三酯水平。结果:与Apo E~(-/-)小鼠比较,Adamts13~(-/-)Apo E~(-/-)小鼠的动脉粥样硬化病变显著增加(P <0. 05);与Apo E~(-/-)小鼠或者野生型小鼠相比较,Adamts13~(-/-)Apo E~(-/-)和Adamts13~(-/-)小鼠血浆中超大分子VWF多聚体(UL-VWF多聚体)明显增加(P <0. 01),血脂结果显示Adamts13~(-/-)Apo E~(-/-)小鼠血浆高密度脂蛋白水平高于Apo E~(-/-)小鼠(P <0. 05)。结论:ADAMTS13可能通过降解UL-VWF多聚体,抑制血小板聚集和炎症反应,从而减慢动脉粥样硬化发展中的进程。
Objective: To observe the effect of Von Willebrand factor-cleaving protease,a disintegrin and metalloprotease with a thrombospondin type 1 motif,member 13( ADAMTS13) on model mice with atherosclerosis( AS),and to evaluate its mechanism. Methods: Adamts13~(-/-)ApoE~(-/-)and ApoE~(-/-)mice were fed with a high-fat western diet for 12 weeks. Whole blood was collected via retro-orbital sinus plexus from the mice with 3. 9% sodium citrate anticoagulant tube for plasma lipid analyses. The extent of atherosclerotic lesions in the aorta was quantified with Oil Red O staining. The heart was then sectioned and stained with hematoxylin and eosin. And histological examination of atherosclerotic lesions in heart was performed. Plasma Adamts13 activity and von willebrand factor( VWF) multimer levels in mice were detected and analyzed. Results: Plasma VWF multimer analysis via Western blot showed that the ratio of ultra large-von willebrand factor( UL-VWF) to low-molecular-weight vWF multimers in the Adamts13~(-/-)ApoE~(-/-)mice increased as compared with ApoE~(-/-)mice. The plasma Adamts13 activity decreased in Adamts13~(-/-)ApoE~(-/-)mice. Conclusion: ADAMTS13 plays a critical role in modulating the development of early atherosclerosis,maybe through the proteolytic cleavage of UL-VWF multimers,accordingly inhibiting platelet deposition and inflammation.

关键词(KeyWords)： 动脉粥样硬化;载脂蛋白E类;血小板;血管性血友病因子裂解酶13;血管性血友病因子
atherosclerosis(AS);apolipoproteins E(ApoE);blood platelets;a disintegrin and metalloproteinase with a thrombospond in type 1 motif,member 13(ADAMTS13);von willebrand factor(VWF)

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(81660026);; 吉林省教育厅“十三五”科学技术研究项目[吉教科合字(2016)273]

作者(Author): 李华,李鸿雁,金圣宇
LI Hua,LI Hongyan,JIN Shengyu

DOI: 10.19367/j.cnki.2096-8388.2020.12.006

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