利拉鲁肽对ApoE基因缺陷小鼠动脉粥样硬化及相关危险因素的影响

Effects of glucagon like peptide- 1 analogue, liraglutide, on atherosclerosis in ApoE deficient mice

目的观察长效胰高糖素样肽-1类似物利拉鲁肽对Apo E基因缺陷小鼠动脉粥样硬化及相关血清学指标的影响。方法高脂饲料喂养Apo E基因缺陷小鼠诱导动脉粥样硬化形成,并随机分为对照组(不给药,n=11)和利拉鲁肽组(30μg·d-1,皮下注射,共4周,n=12)。比较两组小鼠主动脉粥样硬化斑块面积/管腔面积、内膜厚度/中膜厚度、血脂、血清一氧化氮(NO)、肿瘤坏死因子α(TNF-α)、丙二醛(MDA)水平。结果对照组和利拉鲁肽组小鼠斑块面积/管腔面积、内膜厚度/中膜厚度无显著差异(P>0.05),两组中体重增加在中位数以下的小鼠进行亚组比较,利拉鲁肽组斑块面积/管腔面积、内膜厚度/中膜厚度均显著下降(P<0.05)。利拉鲁肽组总胆固醇、三酰甘油、低密度脂蛋白胆固醇、TNF-α水平显著低于对照组(P<0.05),NO水平显著高于对照组(P<0.05),两组间MDA水平无显著差异(P>0.05)。结论利拉鲁肽具有减轻体重、改善血脂水平,保护内皮功能及抑制炎症反应等作用,并可能通过减轻体重发挥潜在的抗动脉粥样硬化作用。

AIM To investigate the effects of long active glucagon-like peptide- 1 analogue, liraglutide, on atherosclerosis and related serum indicators in ApoE deficient mice. METHODS ApoE deficient mice, fed with high-fat-diet to establish atherosclerotic model, were randomly divided into control group （noadminstration, n ~ 11） and liraglutide group （30 jxg per day, injected subcutaneously for 4 weeks, n = 12）. The aorta was separated and the area ratio of plaque and lumen, the thickness ratio of endangium and tunica media were analyzed. The levels of serum lipid, NO, tumor necrosis , factor- α （TNF- α）, malondialdehyde （MDA） were also measured. RESULTS There were no significant difference between the two groups in the area ratio of plaque and lumen, the thickness ratio of endangium and tunica media （P 〉 0.05）. But when compared in the mice with body weight increase blow the median of the two groups （P 〈 0.05） , the above ratios were significant decreased in the liraglutide group （P 〈 0.05）. The levels of serum TC, LG, LDL-C, NO, TNF-α of liraglutide group were significant lower than the control group （P 〈 0.05）. There was no difference between two groups in MDA levels （P 〉 0.05）. CONCLUSION Liraglutide may be able to reduce weight, improve lipid metabolism, protect endothelial function and inhibit inflammation in ApoE deficient mice. Through reducing weight, liraglutide may inhibit atherosclerosis progress.