他汀升高大鼠载脂蛋白A5降低甘油三酯的机制

Statin reduced triglyceride level via activating peroxisome proliferstor activated receptor α and upregulating apolipoprotein A5 in hypertriglyceridemic rats

目的 明确他汀降低甘油三酯（TG）作用是否与载脂蛋白A5（ApoA5）有关,探讨他汀调节ApoA5的机制.方法 24只Sprague-Dawley大鼠随机分为3组：（1）对照组（n=8）：正常普通饮食喂养;（2）高甘油三酯血症（HTG）组（n=8）：10%果糖水喂养2周建立HTG大鼠模型,并继续喂养4周;（3）他汀组（n=8）：HTG大鼠建模后,加予阿托伐他汀（10 mg·kg^-1·d^-1）干预4周.测定空腹血脂及肝脏ApoA5和过氧化物酶体增殖物激活受体α（PPARα）表达.体外观察阿托伐他汀对HepG2细胞TG、ApoA5和PPARα的影响,并检测PPARα抑制剂是否影响他汀的上述效应.结果 （1）6周后,HTG组大鼠TG显著高于对照组,而他汀组TG则显著低于HTG组（P均〈0.05）.（2）HTG组大鼠ApoA5表达显著低于对照组,而他汀组的ApoA5表达则显著高于HTG组（P均〈0.05）.（3）HTG组大鼠PPARα的mRNA表达显著低于对照组,而他汀组PPARα mRNA表达显著高于HTG组（P均〈0.05）.结论 他汀显著升高肝细胞ApoA5和PPARα表达,降低细胞TG含量,但PPARα抑制剂可以显著抑制他汀的上述效应.他汀通过PPARα通路,上调ApoA5表达,降低TG.

Objective To explore the potential role of apolipoprotein A5 （apoAS） on the hypertriglyceridemia （HTG）-lowering effects of statin. Methods Twenty-four Sprague-Dawley rats were randomized into 3 groups ： （ 1 ） control group （ n = 8 ） , with no special treatment; （ 2 ） HTG group （ n = 8 ） , treated with 10% fructose water for 6 weeks; （3） statin group（n =8）, treated with 10% fructose water for 2 weeks and eotreated with atorvastatin 10 mg· kg^-1 · d^- 1 for another 4 weeks. Body weight, fasting plasma lipids and the hepatic expressions of apoA5 and peroxisome prolfferstor activated receptor （PPAR） ot were determined. In separate in vitro experiments, we tested the effects of atorvastatin on TG and the expressions of apoA5 and PPARα in HepG2 cells. Results （ 1 ） At 6 weeks, plasma TG was higher in rats in HTG group than in controls, which was significantly reduced in statin group （ both P 〈 0. 05 ）. （2） Rat hepatic apoA5 expression in HTG group was significantly lower than in control group and was significantly higher in statin group than in HTG group （both P 〈0. 05）. （3） Similarly, rat PPARα mRNA expression in HTG group was lower than in control group and was higher in statin group than in HTG group （ both P 〈 0. 05 ）. （4） Statin significantly upregulated the expressions of apoA5 and PPARα and decreased TG in HepG2 ceils. The above effects induced by statin was blocked in the presence of PPARα inhibitor. Conclusions Upregnlation of apoA5 expression contributes to TG lowering effect of statin via PPARα signaling pathway.