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-脱氧寡核苷酸(OX-PS-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′s指数、血糖、胰岛素、甘油三酯、总胆固醇高于对照组(P〈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(P〈0.05),且OX1R的表达量与Lee′s指数、血糖、胰岛素、甘油三酯、总胆固醇呈显著负相关(r分别为-0.829,-0.710,-0.801,-0.733和-0.756)。OX-PS-ODNs干预下丘脑orexin系统2d后,营养性肥胖大鼠肾上腺皮质中OX1R的表达明显下降(P〈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-垂体-肾上腺(HPA)轴参与调控能量代谢。
Objective 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 (P 〈 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 (P 〈 0.05),and negatively correlated with Lee′s index,blood glucose,insulin,triglycerides and total cholesterol (P 〈 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 involved in the regulation of modelate-energy metabolism via hypothalamic- pituitary- adrenal(HPA) axis in dietary obese rats.