高同型半胱氨酸血症致LDLr^(-/-)小鼠动脉粥样硬化形成和加重的研究

Hyperhomocysteinemia promotes and accelerates atherosclerosis in low-density lipoprotein receptor knock-out mice

目的探讨高同型半胱氨酸血症对低密度脂蛋白受体基因敲除(LDLr^(-/-))小鼠动脉粥样硬化形成的影响。方法48只7周龄LDLr^(-/-)小鼠分为高蛋氨酸组、高脂组、高蛋氨酸高脂组和对照组,分别喂食高蛋氨酸饲料、高脂饲料、高蛋氨酸高脂饲料和标准饲料。在小鼠第19、23和27周龄时,每组分别处死4只小鼠并进行检测血样中的TC、TG、LDL-C和同型半胱氨酸(Hcy)水平,并测定主动脉窦部及内膜面粥样硬化面积。结果在小鼠第19、23和27周龄时,高蛋氨酸组和高蛋氨酸高脂组小鼠血清中Hcy水平较高脂组和对照组水平高(均P<0.01),高脂组和高蛋氨酸高脂组小鼠血清TC、TG和LDL-C水平较高蛋氨酸组和对照组水平高(均P<0.01);相比对照组小鼠在第27周龄时于主动脉窦部及内膜面形成动脉粥样硬化,其它3组小鼠第19周龄时即有动脉粥样硬化形成,其中高蛋氨酸组动脉粥样硬化程度较高脂组轻,而高蛋氨酸高脂组最重(P<0.05)。结论高Hcy血症可导致LDLr^(-/-)小鼠动脉粥样硬化形成和加重。

Objective To investigate the influence of hyperhomocysteinemia on the development of atherosclerosis inlow-density lipoprotein(LDL)receptor knock-out mice(LDLr-/-).Methods Forty-eight7-week-old LDLr-/-mice wererandomly assigned to methionine group,fat group,methionine-fat group and control group,and fed high-methionine diet,high-fat diet,high methionine and fat diet,and a standard rodent diet,respectively.At the age of19weeks,23weeks and27weeks,four mice per group were sacrificed respectively.The levels of total cholesterol(TC),triglyceride(TG),low densitylipoprotein cholesterol(LDL-C)and homocysteine(Hcy)were measured,atherosclerotic areas in aortic sinus and intimawere calculated.Results Serum homocysteine was significantly higher in methionine group and methionine-fat groupthan in fat group and control group(all P<0.01),TC,TG,and LDL-C were significantly higher in fat group andmethionine-fat group than in methionine group and control group(all P<0.01)at the age of19weeks,23weeks and27weeks.Atherosclerosis developed in aortic sinus and aortic intima at the age of27weeks in control group and at the ageof19weeks in other three groups.The extent of atherosclerotic lesion was less in methionine group than in fat group,andlargest in methionine-fat group(P<0.05).Conclusion Hyperhomocysteinemia may promotes and accelerates thedevelopment of atherosclerosis in LDLr-/-mice.