ApoCⅢ转基因引起的高血浆甘油三酯对弹力蛋白酶诱导的LDLR^(-/-)小鼠腹主动脉瘤的影响

Effects of high plasma triglyceride caused by ApoC Ⅲ transgene on abdominal aortic aneurysm induced by elastase in LDLR^(-/-) mice

目的:研究载脂蛋白CⅢ(Apo CⅢ)转基因引起的高血浆甘油三酯(TG)对腹主动脉瘤发生发展的影响。方法:以LDLR^(-/-)和Apo CⅢ+LDLR^(-/-)小鼠喂饲高脂饲料,分别造成高胆固醇血症和高胆固醇合并高甘油三酯血症模型;采用弹力蛋白酶法在2种基因型小鼠上诱导建立腹主动脉瘤模型;以动脉瘤发生率、动脉瘤直径、主动脉弹力板降解情况及血管基质金属蛋白酶的表达等为指标,比较LDLR^(-/-)和Apo CⅢ+LDLR^(-/-)小鼠分别在普通饲料和高脂饲料喂饲条件下,腹主动脉瘤的发生和发展情况;采用TNF-α诱导血管平滑肌细胞(VSMC)建立动脉瘤体外微环境模型,研究来自具有正常含量Apo CⅢ或高含量Apo CⅢ小鼠的富含甘油三酯的脂蛋白(TRLs)对弹力蛋白表达的影响。结果:高脂饲料加重了LDLR^(-/-)小鼠的腹主动脉瘤程度;高脂饲料喂饲的Apo CⅢ+LDLR^(-/-)小鼠腹主动脉瘤轻于高脂喂饲的LDLR^(-/-)小鼠;在体外,TRLs具有抑制TNF-α诱导的VSMC弹力蛋白酶降解的作用,且来自高含量Apo CⅢ小鼠的TRLs对弹力蛋白降解的抑制作用更为显著。结论:Apo CⅢ转基因引起的高血浆甘油三酯能减轻弹力蛋白酶诱导的LDLR^(-/-)小鼠的腹主动脉瘤,该作用可能与Apo CⅢ基因及其导致的高血浆甘油三酯有关。

AIM： To investigate the effects of high plasma triglyceride（ TG） caused by apolipoprotein C Ⅲ（ Apo CⅢ） transgene on the occurrence and development of abdominal aortic aneurysm（ AAA）. METHODS： The animal models of hypercholesterolemia and hypercholesterolemia combined with hypertriglyceridemia were established by feeding high-fat diet to LDLR^（-/-）and Apo CⅢ＋LDLR^（-/-）mice,respectively. AAA was induced in these mice by pancreatic elastase.By evaluating the incidence of AAA,relative maximal abdominal aortic diameter,disruption of the elastic lamellar structure and expression of matrix metalloproteinases（ MMPs） in the aorta walls of the AAA,the occurrence and development of AAA were compared in LDLR^（-/-）and Apo C Ⅲ＋LDLR^（-/-）mice fed with either chow diet or high-fat diet. In addition,an in vitro TNF-α-induced aneurysmal microenvironment model on vascular smooth muscle cells（ VSMC） was used to study the impact of triglyceride-rich lipoproteins（ TRLs） from mice with normal or high contents of Apo CⅢ on elastin protein expression. RESULTS： Feeding the high-fat diet aggravated the severity of AAA in the LDLR^（-/-）mice. Apo CⅢ＋LDLR^（-/-）mice fed with high-fat diet had less severe AAA than LDLR^（-/-）mice fed with high-fat diet. TRLs inhibited degradation of VSMC elastin protein induced by TNF-α,and in vitro TRLs from the mice with high content of Apo CⅢ,compared to those with normal content of Apo CⅢ,had better inhibitory effect on the degradation of elastin. CONCLUSION： High plasma TG caused by Apo CⅢ transgene alleviates AAA of the LDLR^（-/-）mice induced by elastase and high-fat diet. The effect is probably attributed to the hypertriglyceridemia caused by Apo CⅢ transgene.