激活PPARα缓解PPARγ诱导的小鼠脂肪肝  

Activation of PPARα improves PPARγ-induced fatty liver in the mouse

作　　者：白亮[1,2] 王蓉[1,2] 罗肖[3] 赵四海[1,2] 刘恩岐[1,2] 

机构地区：[1]西安交通大学医学部心血管研究中心动脉粥样硬化与脂代谢研究室,西安710061 [2]西安交通大学医学部医学实验动物中心,西安710061 [3]西安交通大学医学部基础医学院生理学与病理生理学系,西安710061

出　　处：《中国实验动物学报》2015年第4期342-346,共5页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金(No.81200207);中央高校基本科研业务费专项资金资助项目

摘　　要：目的研究PPARα激活后对PPARγ诱导小鼠脂肪肝的影响。方法以4~5周龄C57BL/6J小鼠为模型,实验分为4组：正常饮食组;0.125%Wy-14,643处理组;PPARγ腺病毒（Ad/PPARγ）注射组;先给予0.125%Wy-14,643饮食再注射Ad/PPARγ组。实验结束时,收集肝脏组织称重、照相,H＆E、油红O染色观察PPARα激活后对PPARγ诱导肝脏脂肪变性的影响。结果野生型小鼠给予PPARα激动剂Wy-14,643处理8 d,与对照组相比,处理组小鼠肝脏明显增大,呈现过氧化物酶体增殖反应;野生型小鼠给予Ad/PPARγ5 d,小鼠肝脏显著增大,出现脂肪肝;给予PPARα激动剂Wy-14,643 3 d,再给予Ad/PPARγ5 d,小鼠肝脏增大更加显著,H＆E染色、油红O染色结果显示小鼠肝脏脂肪变性明显减轻。结论激活PPARα能够缓解PPARγ诱导的小鼠肝脏脂肪变,为脂肪肝的预防和治疗提供了新的研究思路和靶点。Object To investigate the effect of PPARα activation on PPARγ-induced fatty liver in the mouse.Methods Wild type mice（ C57 BL /6） aged 4 to 5 weeks were used as animal models. All mice were divided into four groups. The mice in the first group were fed with chow diet. The mice in the second group were fed with a diet containing0. 125% Wy-14,643,an agonist of PPARa,for 8 days. The mice in the third group were injected with Ad / PPARγ via tail vein for 5 day. The mice in the fourth group were firstly fed with Wy-14,643 diet for 3 days and then injected with Ad /PPARγ via tail vein for another 5 day. Mouse livers were collected and photographed. The effect of PPARα activation on PPARγ-induced fatty liver was observed by HE and Oil red O staining. Results Compared with the controls,wild-type mice treated with Wy-14,643 for 8 days exhibited marked hypertrophy of hepatocytes with increased cytoplasmic eosinophilia and proliferation of peroxisomes. The liver size was significantly increased in the wild-type mice treated with Ad / PPARγfor 5 days,and over-expression of PPARγ strongly induced hepatic steatosis. Importantly,the wild-type mice pretreated with Wy-14,643 for 3 days and then given Ad / PPARγ injection exhibited dramatically the increase of liver size,which might be due to the dual function of PPARa and PPARγ. Compared with the Ad / PPARγ group,the Wy-14,643 pretreatment group showed a reduced hepatic steatosis. Conclusions Activation of PPARα by Wy-14,643 effectively improves PPARγ-stimulated hepatic steatosis,which provides a novel target for prevention and therapy of fatty liver.

关 键 词：脂肪肝 PPARa PPARΓ 小鼠 

分 类 号：Q95-33[生物学—动物学]