HUANG Xian-sheng, ZHAO Shui-ping, BAI Lin, ZHANG Qian, HU Min, ZHAO Wang
Department of Cardiology, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2010 Sep;38(9):809-13.
to explore the potential role of apolipoprotein A5 (apoA5) on the hypertriglyceridemia (HTG)-lowering effects of statin.
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 cotreated 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 proliferator activated receptor (PPAR)α 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.
(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 cells. The above effects induced by statin was blocked in the presence of PPARα inhibitor.
upregulation of apoA5 expression contributes to TG lowering effect of statin via PPARα signaling pathway.
探讨载脂蛋白A5（apoA5）在他汀类药物降低高甘油三酯血症（HTG）作用中的潜在作用。
将24只Sprague-Dawley大鼠随机分为3组：（1）对照组（n = 8），不进行特殊处理；（2）HTG组（n = 8），用10%果糖水治疗6周；（3）他汀组（n = 8），先用10%果糖水治疗2周，再联合阿托伐他汀10 mg×kg⁻¹×d⁻¹治疗4周。测定体重、空腹血脂以及肝脏中apoA5和过氧化物酶体增殖物激活受体（PPAR）α的表达。在单独的体外实验中，我们检测了阿托伐他汀对HepG2细胞中甘油三酯（TG）以及apoA5和PPARα表达的影响。
（1）6周时，HTG组大鼠血浆TG高于对照组，他汀组显著降低（均P < 0.05）。（2）HTG组大鼠肝脏apoA5表达显著低于对照组，他汀组显著高于HTG组（均P < 0.05）。（3）同样，HTG组大鼠PPARα mRNA表达低于对照组，他汀组高于HTG组（均P < 0.05）。（4）他汀显著上调HepG2细胞中apoA5和PPARα的表达并降低TG。在存在PPARα抑制剂的情况下，他汀诱导的上述作用被阻断。
apoA5表达上调通过PPARα信号通路有助于他汀类药物降低TG的作用。
