Ghrelin对大鼠摄食的影响及orexins信号通路的调控

目的:探究Ghrelin对大鼠摄食的影响及orexins信号通路的调控作用。方法:采用免疫组织化学染色的方法观察Ghrelin免疫阳性神经元轴突末梢与orexin神经元的突触联系以及下丘脑外侧区(LHA)内c-fos的表达。侧脑室注射抗-orexin-A IgG和抗-orexin-B IgG混合液、抗-黑色素浓集激素(MCH)IgG、NPY-1受体拮抗剂后测量大鼠摄食量,观察其对ghrelin诱导摄食的影响。结果:Ghrelin免疫阳性神经元轴突末梢与orexin神经元的突触相接触。侧脑室注射ghrelin可诱导orexin神经元内c-fos表达,但是没有引起MCH神经元内c-fos的表达。预先注射抗-NPY IgG抗体,ghrelin仍然可诱导orexin神经元内c-fos表达。侧脑室预先注射抗-orexin-A IgG和抗-orexin-B IgG抗体可减弱ghrelin促摄食作用,但是预先注射抗-MCH IgG抗体对ghrelin诱导的摄食作用没有明显影响。注射NPY受体拮抗剂可进一步加强抗-orexin-A IgG抗体和抗-orexin-B IgG抗体对ghrelin诱导摄食的抑制效应。结论:ghrelin可能与orexin系统相互作用共同参与摄食和能量平衡的调控。

Effect of Ghrelin on the Feeding of Rats and Regulation of Orexins Signaling Pathway

ABSTRACT Objective: To investigate the effect of ghrelin on the feeding of rats and the regulation of orexins signaling pathway. Methods: Immunohistochemical staining was used to observe the synaptic connections of ghrelin immunoreactive neurons axon terminals and orexin-producing and the expression of c-fos in hypothalamic lateral area (LHA). After intracerebroventricular injection of anti-orex- in-A IgG and anti-orexin-B IgG, anti- melanin-concentrating hormone (MCH) IgG, NPY-1 receptor antagonist, food intake was measured to observe its effect on ghrelin-induced food intake. Results: Ghrelin-immunoreactive axonal terminals made direct synaptic contacts with orexin-producing neurons. Intracerebroventricular administration of ghrelin induced c-fos expression in orexin-producing neurons but not in MCH-producing neurons. Pre-injection of anti-NPY IgG antibody, ghrelin still induced c-fos expression in orexin -producing neurons. Pretreatment with anti-orexin-A IgG and anti-orexin-B IgG, but not anti-MCH IgG, attenuated ghrelin-induced feeding. Administration of NPY receptor antagonist further attenuated ghrelin-induced feeding in rats treated with anti-orexinA-IgG and anti-orexinB-IgG. Conclusion: ghrelin may interact with the orexins system to participate in the regulation of feeding behavior and energy homeostasis.