胰岛素抵抗大鼠 Orexin/leptin系统变化及其影响因素的研究

目的研究IR大鼠下丘脑及脂肪组织中orexin和leptin系统的变化,分析其可能的调控因素.方法IR大鼠模型采用高脂肪膳食诱导并经钳夹技术证实;RT-PCR技术检测orexin/leptin及其受体(OX1R、OX2R、LR)mRNA的表达;生化比色法测定血清FFA、放免法测定血清TNF-α.结果该模型大鼠下丘脑中Prepro-orexin表达减少约80%,OX1R、OX2R分别增加3.4及3.2倍,leptin mRNA增加约8倍;LR减少78%;血清FFA和TNF-α均升高;钳夹技术中葡萄糖输注率(GIR60-120)明显低于对照组.结论高脂肪膳食可诱导大鼠体内IR;并导致orexin/leptin系统平衡状态的破坏;orexin与leptin相互作用共同维持机体能量代谢的稳定:FFA和TNF-α可能参与该系统的调控.

Study of orexin/leptin system change and influencing factors in insulin-resistant rats

Objective: To investigate the change of orexin and leptin system in hypothalamus and adipose tissue of insulin-resistant (IR) rats and analyze the regulatory factors. Methods: IR rat model was induced by fat-rich diet and approved by glucose clamp technique. RT-PCR was used to detect the expression of orexin/leptin and the receptor (OX1R, OX2R, LR) nRNAs while biochemical colorimetry was used for serum FFA detection and radioimmune assay for serum TNF-α. Resnlts: In the hypothalamus of the IR rat model, zthe expression of prepro-orexin decreased by 80%. OX1R, OX2R increased by 3.4 folds and 3.2 folds respectively. Leptin mRNA increased by approximately 8 folds and LR reduced by 78%. Both serum FFA and TNF-α evidently increased and glucose infusion rate (GIR60-120) during glucose clamp was markedly lower than.that in control group. Conclusions: Fat-rich diet can induce insulin resistance in rats and disturb the balance of orexin/leptin systen. The interaction between orexin and leptin maintains the stability of energy metabolism in the body. FFA and TNF-α may also play a part in the regulation of orexin/leptin system.