Objective To investigate the role of PPARa in NASH and IR of SD rats and the mechanisms in insulin resistance way. Methods 60 male SD rats were randomly divided into four groups: normal chow-fed control group ( re =20 );high fat-fed group ( re =20 );experimental group ( re = 10 );experimental control group ( re = 10 ). At the end of 12th week,each 10 rats which randomly selected form normal control group and the high fat-fed group were put into glucose clamp test and liver tissue HE staining to ensure the model succeeded. Then they were given normal chow-fed,fenofibrate and continue high-fat diet intervention, which took four weeks in all. Aminotransferase, triglyceride were measured by biochemical methods, and the mRNA expression level of PPARa genes were detected by the reverse transcriptase-polymerase chain reaction ( RT-PCR ) technique. Results Hyperlipidemia was observed in high fat-fed groups rats. Compared with normal chow-fed controls groups, PPARa mRNA expression was down-regulation( P < 0. 05 ), the steatosis and inflammatory activity in the livers and the insulin resistance were significantly increased( P <0. 05 );Compared with the high fat-fed group,PPARa mRNA expression in experimental group and experimental control group was up-regulation( P <0. 05 ),and the insulin resistance were significantly decreased. Conclusion PPARa' s mRNA is positively correlated with the IR. It is effective in cure of the rat' s NASH and IR after using the PPARa agonists.%目的 研究PPARα在SD大鼠NASH、IR的形成中的作用,并初步从胰岛素抵抗方面探讨其机制.方法 将SD大鼠60只随机分为正常组20只、高脂组20只、实验组10只(高脂加非诺贝特)、实验对照组10只(造模成功后改正常饮食).饲养12周末时随机取正常对照组与高脂组各10只一并做高胰岛素正葡萄糖钳夹实验及肝组织的HE染色,确定造模成功.然后给予非诺贝特、继续高脂饮食及改正常饮食干预,共4周.氨基转移酶、三酰甘油等以生物化学方法测定,并以逆转录-聚合酶链反应(RT-PCR)技术分析PPARα基因的mRNA表达水平.结果 高脂组大鼠呈高脂血症,与正常组相比PPARα的mRNA表达下调(P<0.05),胰岛素抵抗(IR)和肝细胞脂肪变及炎症程度加重(P<0.05);与高脂组比较,实验组及实验对照组的PPARα的mRNA表达上调(P<0.05),IR明显改善.结论 在高脂饮食诱导的NASH、IR模型中,PPARα的mRNA表达水平与IR密切相关,它们可以共同促进NASH的进展,而使用PPARα激动剂后对大鼠NASH及IR起到了有效的治疗作用.
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