普罗布考对小鼠体内巨噬细胞胆固醇逆转运的影响及其作用机制

Effect of probucol on reverse cholesterol transport in mouse macrophages and its mechanism

目的探讨普罗布考对小鼠体内巨噬细胞TC逆转运的影响及其作用机制。方法选择C57BL/6小鼠36只随机分为4组,给予不同剂量普罗布考(0,0.1%,0.5%,1.0%,分别为对照组,0.1%干预组,0.5%干预组,1.0%干预组),各组9只。添加饲料喂养6周后,腹腔注射乙酰化LDL与氚(3 H)-TC标记的RAW264.7小鼠巨噬细胞悬液,酶法测定血脂,用液闪计数仪测定血清、肝脏及粪便中3 H-TC占经腹腔注射3 H-TC的百分比。结果普罗布考干预6周后,与对照组比较,各干预组小鼠TC、HDL-C、LDL-C明显降低(P<0.05,P<0.01),肝脏和粪便中3 H-TC含量明显升高(P<0.05),血清3 H-TC含量明显降低(P<0.05)。各干预组HDL-C水平与3 H-TC排泄量呈负相关(r=-0.532,P<0.05)。结论普罗布考干预了小鼠体内巨噬细胞TC逆转运,加速了TC经粪便的清除,有利于动脉粥样硬化的防治。

Objective To study the effect of probucol on reverse cholesterol transport in mouse macrophages and its mechanism. Methods Thirty six C57BL/6 mice were randomly divided into control group, 0.1% probucol treatment group, 0.5 % probucol treatment group, and 1.0% probucol treatment group（9 in each group）. The mice were intraperitoneally injected with acetylated LDL and 3 H-TC-labled RAW264. 7 macrophage suspecion 6 weeks after fed with chow diet. Their serum lipoid level was measured using enzymatic method. The proportion of intraperitoneally in jected 3 H-TC in serum,liver tissues and feces was assayed with a liquid scintillation counter. Results The serum TC, HDL-C and LDL-C levels were significantly lower in different prohucol treatment groups than in control group 6 weeks after treatment（P〈0.05,P〈0.01）. The 3H TC level was significantly higher in liver and feces, and significantly lower in serum（P〈0.05）. The LDL-C level was negatively related with the 3 H-TC excretion in different probucol treatment groups（r=-0. 532, P〈0.05）. Conclusion Probucol can interfere with the reverse cholesterol transport in mouse macrophages and accelerate the clearance of cholesterol via feces, and is thus beneficial for the prevention and treatment of atherosclerosis.