糖皮质激素对普通大鼠和肥胖大鼠下丘脑AGRP、CART基因表达的影响

Effects of glucocorticoid on Agouti-related peptide and cocaine and amphetamine regulated transcript gene expression in the hypothalamus of nonobese and obese rats

目的:探讨糖皮质激素对普通大鼠和肥胖大鼠下丘脑Agouti相关蛋白(AGRP)和受可卡因和安非他明调节的转录肽(CART)基因表达的影响。方法:肥胖大鼠和普通大鼠分别随机分为生理盐水组(NSG)、小剂量组(LDG)和大剂量组(HDG),连续20天腹腔注射生理盐水0.2ml/100g和琥珀酸氢化可的松5mg/kg、15mg/kg。逆转录实时荧光定量PCR测定下丘脑AGRP和CART mRNA的表达水平。结果:大剂量糖皮质激素可使普通大鼠和肥胖大鼠下丘脑组织中促进食欲肽AGRP mRNA和抑制食欲肽CART mRNA的表达水平显著低于盐水组(P<0.05)。给予小剂量糖皮质激素后,肥胖大鼠下丘脑组织中AGRP和CART mRNA的表达量与生理盐水组相比差异无统计学意义(P>0.05),普通大鼠下丘脑组织中AGPR mRNA的表达水平与生理盐水组明显下降(P<0.05),而普通大鼠CART的表达与生理盐水组无差异。结论:应用大剂量糖皮质激素使肥胖大鼠和普通大鼠下丘脑促进食欲肽AGRP和抑制食欲肽CART mRNA的表达均下降。小剂量糖皮质激素使普通大鼠下丘脑促食欲神经肽AGRP mRNA的表达下降。

Objective：To investigate the effect of glucocorticoid on expression of hypothalamic Agouti-related peptide（AGRP）,and cocaine and amphetamine regulated transcript（CART）in normal and obese rats.Methods：Both normal and obese SD rats were randomly assigned to 3 groups：normal salina group（NSG）,low dose glucocorticoid group（LDG）and high dose glucocorticoid group（HDG）,and intraperitoneal injection with normal saline 0.2 ml/100 g,hydrocortisone sodium succinate 5 mg/kg and 15 mg/kg for 20 days.Real-time RT-PCR was used to measure the expression of AGRP,CART mRNA in hypothalamus.Results：After high dose glucocorticoid injection,the mRNA expressions of orexigenic neuropeptide AGRP and anorexigenic neuropeptide CART,were significantly lower than the NSG in hypothalamus of both obese and normal rats（P〈0.05）.After low dose glucocorticoid injection,there were no differences of hypothalamic AGRP,CART mRNA expressions from the NSG in obese rats.In normal rats,the expressions of AGRP mRNA were significantly lower than those of the NSG after low dose glucocorticoid injection（P〈0.05）while no difference of CART mRNA from the NSG.Conclusions：High dose glucocorticoid downregulated orexigenic neuropeptide AGRP and anorexigenic neuropeptide CART mRNA expression levels in hypothalamus of obese and normal rats.Low dose glucocorticoid downregulated orexigenic neuropeptide AGRP mRNA expression in hypothalamus of normal rats.