下丘脑室旁核外源性orexin-A对肥胖大鼠摄食的影响及NPY受体信号的调控

Effect of hypothalamic PVN exogenous orexin-A on food intake in obese rats and regulation by NPY receptor signaling pathway

目的:探讨饮食诱导肥胖(DIO)大鼠神经肽Y(NPY)受体信号通路是否参与下丘脑室旁核(PVN)外源性注射食欲素A(orexin-A)对摄食和葡萄糖敏感(GS)神经元兴奋性的调控。方法:采用荧光免疫组织化学实验观察PVN中orexin-A受体(即食欲素1型受体,OX1R)和NPY受体Y5(NPY-5R)的表达;采用单细胞外放电记录观察orexin-A对PVN内GS神经元兴奋性的影响;分别于SD大鼠和DIO大鼠PVN埋置套管,经套管注射orexinA、OX1R拮抗剂SB-334867和NPY-5R拮抗剂CGP-71683,观察大鼠0~2 h和0~4 h摄食量。结果:DIO大鼠PVN中OX1R和NPY-5R的表达显著高于SD大鼠。Orexin-A抑制PVN内葡萄糖抑制性(GI)神经元,兴奋葡萄糖兴奋性(GE)神经元,但是orexin-A对GS神经元的兴奋或抑制效应可被NPY-5R拮抗剂CGP-71683部分阻断,且与SD大鼠相比,orexin-A对DIO大鼠PVN内GS神经元兴奋或抑制效应更加明显。PVN内注射orexin-A可增加SD大鼠和DIO大鼠摄食量。但是orexin-A诱导的促摄食效应被NPY-5R拮抗剂CGP-71683部分阻断。与SD大鼠相比,orexin-A诱导的促摄食效应在DIO大鼠中更加明显。结论:PVN内外源性注射orexin-A可能主要通过OX1R信号通路参与大鼠摄食和GS神经元兴奋性调控,NPY-5R信号也参与了该过程调控,在DIO大鼠中更敏感。

AIM： To investigate whether neuropeptide Y（ NPY） receptor signaling pathway is involved in the regulation of orexin-A on food intake and glucose-sensitive（ GS） neuronal excitability in the hypothalamic paraventricular nucleus（ PVN） of diet-induced obese（ DIO） rats. METHODS： Fluorescence immunohistochemistry experiment was used to observe the expression of orexin-A receptor（ orexin receptor 1,OX1 R） and NPY receptor Y5（ NPY-5 R） in the PVN.The effect of orexin-A on the excitability of GS neurons in PVN was observed by single cell discharge recording. The cannula was implanted into the PVN of SD rats and DIO rats. The orexin-A,OX1 R antagonist SB-334867 and NPY-5 R antagonist CGP-71683 were injected through the cannula to observe the 0 ~ 2 h and 0 ~ 4 h food intake of the rats. RESULTS： The expression of OX1 R and NPY-5 R in the PVN of DIO rats was significantly higher than that in the SD rats. Orexin-A inhibited glucose-inhibited（ GI） neurons and excited glucose-excited（ GE） neurons in the PVN. However,the effects of orexinA on GS neurons were partially blocked by the NPY-5 R antagonist CGP-71683. Compared with the SD rats,orexin-A had more pronounced excitatory and inhibitory effects on PVN GS neurons in the DIO rats. Injection of orexin-A in the PVN increased food intake in the SD rats and DIO rats. However,the orexin-A-induced feeding was partially blocked by the NPY-5 R antagonist CGP-71683. The effect of orexin-A on feeding was stronger in the DIO rats than that in the SD rats. CONCLUSION： The hypothalamic PVN orexin-A regulates food intake and GS neuronal excitability mainly through the OX1 R signaling pathway,and NPY-5 R signaling is also involved in this process,in which the regulatory effect on DIO rats is more sensitive.