苯扎贝特促进小鼠体内胆固醇逆转运的研究

目的：检测苯扎贝特干预后小鼠血脂浓度，以及血清、肝脏及粪便中3H-胆固醇占经腹腔注射3H-胆固醇总量的百分比，探讨苯扎贝特对小鼠体内胆固醇逆转运的影响。方法35只 C57BL/6小鼠随机分为5组，分别给予普通饲料、不同剂量的苯扎贝特（0.1%、0.25%、0.5%、0.75%）添加普通饲料喂养4周后，腹腔注射经 ac-LDL 及3H-胆固醇处理过的小鼠巨噬细胞悬液（0.5 mL/鼠，细胞数达5.0×106），单独笼养24h 后取血，酶法测定血脂；测定血清、肝脏和粪便中的3H-胆固醇含量（占注射总量的百分比）。结果不同剂量苯扎贝特（0.1%、0.25%、0.5%、0.75%）干预小鼠后，高密度脂蛋白胆固醇（HDL-C）升高并呈剂量相关性趋势。0.75%苯扎贝特组 HDL-C 水平较对照组明显增高，增幅为30.3%；血清甘油三酯（TG）水平较对照组明显降低，降幅为40.3%。苯扎贝特干预各组（0.1%、0.25%、0.5%、0.75%）小鼠血清、肝脏、粪便3H 的总含量显著增多，苯扎贝特干预组（0.1%、0.25%、0.5%、0.75%）小鼠粪便3H-胆固醇含量较对照组增幅分别为＋1.11，＋1.40，+1.60，+1.70倍。结论苯扎贝特剂量依赖性增加 HDL-C 和降低 TG，能加速胆固醇由粪便清除，促进体内胆固醇逆转运，利于动脉粥样硬化的防治。

Benzafibrate promotes reverse cholesterol transport from macrophage to feces in mice in vivo

[Abtract] Objective This study is to observe affect of benzafibrate on serum paraoxonase-1 activity in mice during the acute phase response and to investigate the mechanism by which it has anti-oxidized effect. Serum lipid profiles of mice were tested after bezafibrate ad ministration. The 3H-cholesterol contents in serum, liver and feces in mice were measured to explore the effect of bezafibrate on reverse cholesterol transport from macrophage to feces in vivo. Methods 35 male C57BL/6 mice were rando mLy divided into four groups and treated with ordinary diet or plus different dosage (0.1%、0.25%、0.5%、0.75%W/W) of bezafibrate for 4 weeks, then these mice were injected intraperitoneally with 3H-cholesterol-labeled and cholesterol-loaded raw264.7 macrophages (0.5 mL/mice, the amount of cells achieve 5.0×106). Serum lipid profiles were deter mined by enzymatic method. Serum and liver tissues were harvested at 24h, feces were collected. And all samples were analyzed for the appearance of 3H-tracer (as the percentage of the total injected counts). Results 1.Bezafibrate (0.1%、0.25%、0.5%、0.75%) dose-dependently reduced the levels of triglyceride (TG) and increased the level of HDL-C. In contrast to the control, the level of HDL-C was increased by 30.3% while the level of TG was decreased by 40.3% in 0.75% bezafibrate groups. 2. After 24 hours intrapentoneally injected, the 3H-cholesterol levels of serum and liver in the mice treated with different dosage of bezafi-brate (0.1%、0.25%、0.50%、75%) were significantly higher comparing with those in the control. the feces 3H-cholesterol levels in the mice treated with different dosage of bezafibrate (0.1%、0.25%、0.5%、75%) were significantly higher by 110%,140%, 160%,170% comparing with those in the control. Conclusion Bezafibrate significantly and dose-dependently reduces the lev-els of triglyceride (TG) and increases the level of HDL-C; Bezafibrate promotes cholesterol reverse transport in vivo, accelerates clearance of cholesterol via feces, so it will be in favor of the prevention of atherosclerosis.