非酒精性脂肪肝大鼠PPARα基因表达及脂代谢和胰岛素水平的变化

Expression of PPARα and Changes in Lipid Metabolism and Insulin level in the Nonalcoholic Fatty Liver Disease Rats

目的观察非酒精性脂肪肝(NAFLD)大鼠肝组织中PPARα基因的表达,并用PPARα激动剂进行干预,探讨其与胰岛素抵抗、脂代谢紊乱的关系。方法大鼠随机分为①正常对照组、②高脂模型组、③PPARα激动剂干预组,利用高脂饮食建立大鼠非酒精性脂肪肝模型。12周后,检测大鼠血脂、肝功能、血糖、胰岛素水平及胰岛素抵抗指数;RT-PCR法分析PPARα基因的表达;观察肝脏的形态学改变。结果PPARα激动剂可降低NAFLD大鼠转氨酶、血脂水平及胰岛素抵抗指数,可促进NAFLD大鼠中PPARα基因的表达;肝脏形态学明显改善。结论PPARα激动剂能改善NAFLD大鼠脂质代谢紊乱,有明显的保肝降酶作用,具有适度的胰岛素增敏作用。PPARα及其配体在NAFLD发病机制及治疗中的进一步深入研究,将为临床防治NAFLD提供新的思路。

Objective To investigate the expression of peroxisome proliferator-activated receptor α（PPARα） gene in the nonalcoholic fatty liver disease （NAFLD）rats and the relationship among insulin resistance and lipid metabolism with the intervention of PPARα agonist fenofibrate. Methods Rat models of NAFLD were established by high cholesterol feeding and randomly divided into 3 groups： the model group, PPARa agonist group, and a group of normal rats as control. 12 weeks later, the liver function （GOT, GPT）, serum lipid （TG, CHO, HDL-C, LDL-C）, GLU, and insulin level were measured, and the insulin resistance index was calculated. The expression of PPARα gene was measured by reverse transcription-polymerse chain reaction （RT-PCR）, and the pathological alterations in the liver were examined. Results Compared with the model group, GOT, GPT, TG, CHO, LDL-C, insulin and the insulin resistance index were lower, HDL-C was higher, the expression of PPARα gene was enhanced and the liver pathological changes were apparently improved in the PPARα agonist group. Conclusions PPARa agonist can improve lipid metabolism disorder and the sensitivity of insulin in the NAFLD model rats, and protect their liver from aggravation. Further studies are warranted to clarify the mechanism of action of PPARa and its agonist in the pathogenesis of NAFLD, and to explore the possibility of its application in treatment of NAFLD.