高糖输注及罗格列酮干预对大鼠载脂蛋白M表达的影响

目的观察高浓度葡萄糖输注对大鼠载脂蛋白M（apoM）mRNA的表达的影响及罗格列酮干预的作用，并探讨相关机制。方法雄性SD大鼠随机分为5％葡萄糖组（对照组）、25％葡萄糖组（H组）、罗格列酮＋5％葡萄糖组（RN组）、罗格列酮＋25％葡萄糖组（RH组）4组。分两批独立的实验完成，一批应用高胰岛素．正常血糖钳夹（HEC）实验评价葡萄糖输注率（GIR），一批直接取肝脏提取总RNA，检测apoMmRNA表达水平及肝X受体途径（LXR）基因和PPAR-β/δ基因表达情况。结果葡萄糖和罗格列酮对GIR均有影响（均为P〈0．01），并且两者的交互作用差异有统计学意义（P〈0．01）。25％葡萄糖下调大鼠肝脏apoMmRNA表达（P〈0．05），而罗格列酮明显增高大鼠肝脏apoMmRNA的表达（P〈0．0001），但两者的交互作用差异无统计学意义（P〉0．05）。25％葡萄糖显著抑制大鼠肝脏LXR-β（P〈0．01）、SHP1（P〈0．01）、LRH1（P〈0．01）、ABCA1（P〈0．01）、PPAR．13／8（P〈0．01）基因的表达；而罗格列酮仅降低SHP1（P〈0．01）及ABCA1（P〈O．05）基因的表达。罗格列酮显著抑制正常大鼠肝脏ABCA1mRNA的表达（P〈0．05），但在高血糖状态下，罗格列酮则明显升高大鼠肝脏ABCA1mRNA水平（P〈0．01）。双因素方差分析表明罗格列酮和25％葡萄糖对大鼠肝脏ABCA1mRNA影响的交互作用差异有统计学意义（P〈0．01）。结论高浓度葡萄糖和罗格列酮对apoM的调节作用是相对独立的，高浓度葡萄糖有可能主要通过LRH1和（或）ABCA1途径下调apoM基因的表达。

Effect of high concentration glucose infusion and rosiglitazone intervention on the expression of apolipoprotein M in rats

Objective To determine the effect of high concentration glucose infusion and the rosiglitazone intervention on the expression of apolipoprotein M （apoM） in rats, and to explore the underlying mechanisms. Methods Male Sprague Dawley （SD） rats were randomly divided into four groups： 5% glucose group （N group） , 25% glucose group （H group）, rosiglitazone ＋ 5% glucose group （RN group）, and rosiglitazone ＋ 25% glucose group （RH group）. The animal experiments were divided into two separate parts. First, hyperinsulinemic-euglycemic clamp （HEC） test was employed to evaluate glucose infusion rates （GIR）. Second, total RNAs were directly extracted from rat livers and studied for the expression of apoM, liver X receptors （LXR） and PPAR-β/δ. Results Both glucose and rosiglitazone were shown to interfere with GIR （P〈0.01） and the interaction between them also showed significant difference （P〈0.01）. The expression of apoM mRNA in rat liver decreased by 25% glucose infusion （P〈0.05） , and significantly increased by rosiglitazone intervention （P〈0.01）. However, the interaction on apoM mRNA expression between rosiglitazone and glucose was not significant （P〉0.05）. 25% glucose significantly inhibited the expression of LXR-β （P〈0.01）, SHP1 （P〈0.01）, LRH1 （P〈0.01）, ABCA1 （P〈0.01） and PPAR-β/δ （P〈 0.01） in rat liver, while rosiglitazone merely decreased the expression of SHP1 （P〈0.01） and ABCA1 （P〈 0.05）. Rosiglitazone could significantly inhibit liver ABCA1 mRNA expression （P〈0.05） in 51 group rats but significantly increase the liver ABCA1 mRNA level （P〈0.01） in H group rats. Two-way ANOVA showed that the interaction difference between rosiglitazone and 25% glucose on ABCA1 mRNA expression of rat liver was statistically significant （P〈0.01）. Conclusions High concentration glucose and rosiglitazone show independent regulatory effect on apoM. High concentration glucose may down-regulate the expressi