增食欲素受体1在营养性肥胖大鼠肾上腺皮质中的表达及意义

 目的探讨营养性肥胖大鼠肾上腺皮质组织中增食欲素受体1（OX1R）的表达规律，以及下丘脑增食欲素（orexin）系统对其调节作用。方法高脂饮食诱导构建并评估营养性肥胖大鼠动物模型；免疫组化法检测肾上腺皮质组织中OX1R 的表达；侧脑室注射orexin 反义的硫代磷酸化鄄脱氧寡核苷酸（OX鄄PS鄄ODNs）干预下丘脑增食欲素系统，分析肾上腺皮质中OX1R 的变化规律。结果大鼠高脂膳食饲养8 周后，营养性肥胖组大鼠体质量、体脂含量、Lee忆s指数、血糖、胰岛素、甘油三酯、总胆固醇高于对照组（ < 0.05）。OX1R的蛋白表达定位于大鼠肾上腺皮质束状带细胞的细胞质中；与正常对照组相比，营养性肥胖大鼠
肾上腺皮质中的OX1R的表达升高（ < 0.05），且OX1R的表达量与Lee忆s 指数、血糖、胰岛素、甘油三酯、总胆固醇呈显著负相关（ 分别为-0.829，-0.710，-0.801，-0.733和-0.756）。OX鄄PS鄄ODNs干预下丘脑orexin 系统2 d后，营养性肥胖大鼠肾上腺皮质中OX1R的表达明显下降（ < 0.05）。结论大鼠肾上腺皮质束状带细胞的细胞质中有OX1R 的表达，营养性肥胖大鼠体内orexin 系统可能通过下丘脑鄄垂体鄄肾上腺（HPA）轴参与调控能量代谢。

Expression and Significance of Orexin Receptor 1 in the Adrenal Cortex of Diet-induced Obese Rats

To observe the expression of orexin receptor 1（OX1R）in dietary obese rats，and to investigate the regulatory effects of hypothalamus orexin system on OX1R. Methods The diet-induced obese rat models were established and evaluated by feeding a high-fat diet for 8 weeks. Immunohistochemistry was employed to examine the expression of OX1R in adrenal cortex of rats. Lateral ventricular canalization was performed in obese rats，which then received an intra-cerebroventricular injection of OX antisense oligodeoxynucleotide（OX1R-PS-ODNs），in order to intervene hypothalamus orexin system，and to analyze the variation of OX1R. Results There were statistical differences in weight，body fat contents，Lee's index，blood glucose，insulin，triglycerides and total cholesterol between the high-fat diet group and the control group after 8 weeks （ < 0.05）. The OX1R protein appeared in adrenal cortex zona glomerulosa. The expression of OX1R was obviously increased in adrenal cortex of high-fat diet rats（ < 0.05），and negatively correlated with Lee's index，blood glucose，insulin， triglycerides and total cholesterol （ < 0.05）. The correlation coefficient was -0.829，-0.710，-0.801，-0.733 and -0.756 respectively. The amount of OX1R in adrenal cortex of high-fat diet rats was significantly decreased after 2 days of intra-cerebroventricular injection of OX-PS-ODN. Conclusion The expression of OX1R is observed in zona glomerulosa cytoplasm of rat adrenal cortex. Orexin system might be in-volved in theregulation of modelate-energy metabolism via hypothalamic-pituitary-adrenal（HPA）axis in dietary obese rats.