普罗布考对高脂饮食兔胸主动脉内皮功能作用及其机制研究

The Effect and Its Mechanism of Probucol on Endothelial Dysfunction in High-Cholesterol Diet Rabbits

目的 :探讨普罗布考 (Probucol)对高胆固醇饮食兔动脉粥样硬化模型内皮功能的作用及可能作用机制。方法 :成年新西兰白兔 2 6只 (1.5～ 2 .5kg/只 )随机分为 3组 :正常饮食组 (普通饮食 ,n =6 )、高脂饮食组 (高脂饮食 ,n =10 )和普罗布考治疗组(高脂饮食 +普罗布考 2 0 0mg/kg ,n =10 )。在高脂饲养前和饲养后第 12周 ,测血清总胆固醇浓度。第 12周后处死动物 ,检测离体胸主动脉环对乙酰胆碱 (Ach)与硝普钠 (SNP)的反应 ,并测定胸主动脉丙二醛 (MDA)、谷胱甘肽过氧化物酶 (GSH -PX)、总NOS活性。结果 :普罗布考对血脂有明显降低作用 ;和正常饮食组比较 ,高脂饮食组胸主动脉对Ach引起的最大的内皮依赖性舒张 (EDR)反应明显减弱 (0 .16± 0 .0 4vs 0 .6 5± 0 .14 ,P <0 .0 5 ) ,GSH -PX和NOS活性明显降低 (GSH -PX :4 7.5± 2 6 .6vs86 .7± 4 7.6 ,P <0 .0 5 ;NOS :1.0± 0 .2vs 2 .6± 0 .9,P <0 .0 5 ) ,MDA显著增加 (12 .1± 5 .5vs 3.8± 1.9,P <0 .0 5 ) ;而普罗布考组EDR反应较高脂饮食组显著改善 (0 .6 0± 0 .10vs 0 .16± 0 .0 4 ,P <0 .0 5 ) ;GSH -PX和NOS活性明显增加 (GSH -PX :95 .2± 32 .3vs 4 7.5± 2 6 .6 ,P <0 .0 5 ;NOS :2 .8± 1.3vs 1.0± 0 .2 ,P <0 .0 5 ) ,MDA显著增加

Objective: To investigate the effect of pr ob ucol on endothelium-dependent vasodilator activity in high-cholesterol plus high fat diet (HCHF) rabbits and its related medianism. Methods:Twenty-six New Zealand white rabbits (1.5～2.5kg) were r andomized into three groups: Control group (normal diet, n=6), HCHF group (H CHF-diet, n=10) and probucol treated group (HCHF-diet plus probucol 200mg/kg /d, n=10). The plasma total cholesterol (TC) before and after 12-week regime n were analyzed. All the rabbits were sacrificed after the 12th week, the thorac ic aorta was collected to analyze the endothelial function, and the endothelial GSH-PX, MDA and NOS were measured. Results: The level of TC was significantly lowered in the probuc ol treated group than the HCHF group. The endothelium-dependent relaxation (EDR) of aortic rings to acetylcholine (Ach) was significantly damaged in HCHF group (0.16±0.04 vs 0.65±0.14 in control group,P<0.05), but EDR was significant ly preserved in probucol group (0.60±0.10 vs 0.16±0.04, P<0.05). The level of endothelial GSH-PX and NOS activity was significantly lowered in HCFT group, but improved in probucol group. The level of MDA was increased in HCFT group, a nd improved in probucol group. Conclusion:Probucol treatment reduced the TC level and preserved the EDR through its anti-oxidant stress effect.