普罗布考对高同型半胱氨酸血症兔肿瘤坏死因子-α和动脉粥样硬化的影响

摘要

Objective To study the effects of probucol on tumor necrosis factor-alpha ( TNF-α ) and atherosclerosis induced by hyperhomocysteinemia in rabhits. Methods Twenty-four male rabbits were randomly divided into three groups.The control group was fed with common food; the homocysterinemia ( Hcy ) model group was fed with high-methionine food which composed of 1％ methionine;the treatment group was given with high-methionine food and i. g. treated with probucol 1 g · d-1.Blood samples were collected from the ear vein by the end of 20 weeks and we measured the levels of TNF-α and total Hcy ( tHcy). The mRNA expression in ahdominal aorta was measured by RT-PCR. The sections were made for light microscopy to observe the vascular pathomorphological changes. Results The serum levels of TNF-α were ( 4. 01± 1. 13 ) and ( 7. 65 ± 1.73 ) pg · mL-1 in the treatment group and the model group respectively( P＜0. 05 ). The mRNA expression of TNF-α in the treatment group was lower than that in the model group( P＜0. 05 ) , but the plasma levels of Hcy in two groups were not different.Aortic lesion in the treatment group was attenuated compared with that in the model control. Conclusion Probucol could decrease serum TNF-α level but not plasma Hcy. Probucol has an anti-atherosclerosis effect, which is associated with suppressing TNF-α mRNA expression and mitigating endometrial hyperplasia.%目的 观察普罗布考对高同型半胱氨酸(Hcy)血症兔肿瘤坏死因子-α(TNF-α)和动脉粥样硬化的影响.方法 将24只雄性新西兰大耳白兔分成3组,每组8只:正常组给予基础饲料喂养;模型组在基础饲料中加入1%蛋氨酸;治疗组给予高蛋氨酸饮食,从第12周开始灌胃给予普罗布考1 g·d-1.分别于第20周末自兔耳缘静脉取血,检测总同型半胱氨酸和TNF-α.用逆转录-聚合酶链法(RT-PCR)检测腹主动脉中TNF-α的mRNA表达水平,光镜下观察腹主动脉病理形态学变化.结果 治疗组和模型组血清TNF-α水平分别为(4.01±1.13),(7.65±1.73) pg·mL-1(P＜0.05);治疗组腹主动脉TNF-α的mRNA表达水平低于模型组(P＜0.05),血浆同型半胱氨酸水平差异无统计学意义,主动脉病变轻于模型组.结论 普罗布考能降低血清TNF-α水平,但未能降低同型半胱氨酸水平;普罗布考能抑制主动脉TNF-α的mRNA表达水平,减轻内膜增生程度,具有抗动脉粥样硬化作用.