下丘脑Nesfatin-1抑食效应及机制研究

Nesfatin-1 in the Hypothalamus Antifeedant Effect and Mechanism Study

目的:探讨下丘脑nesfatin-1与组胺信号通路间的相互作用及对摄食的影响。方法:采用第三脑室置管、药物注射、免疫组化、ELISA等方法,观察氟甲基组氨酸(FMH)、α螺旋促肾上腺皮质激素释放激素(CRH)和促甲状腺激素释放激素(TRH)对Nesfatin-1诱导的抑制摄食的影响,以及Nesfatin-1与组胺信号通路相互影响调控摄食机制。结果:第三脑室注射nesfatin-1可显著减少大鼠摄食量,而第三脑室内预先注射FMH,nesfatin-1抑制摄食效应明显减弱,但FMH本身并不影响大鼠夜间摄食量。第三脑室注射nesfatin-1,可显著增加优降宁诱发的PVN、腹内侧核(VMH)、结节乳头核(TMN)内t-MH的积累;但腹腔注射nesfatin-1没有引起大鼠摄食改变,t-MH蓄积也无显著变化。第三脑室注射α螺旋CRH或抗TRH血清均可显著减弱nesfatin-1的抑食效应,而α螺旋CRH、抗TRH血清本身并不显著影响大鼠摄食量。第三脑室注射nesfatin-1可显著增加下丘脑PVN内CRH和TRH水平,且nesfatin-1可显著增加优降宁诱导的PVN、VMH和TMN内t-MH的表达,而α螺旋CRH或抗TRH血清可显著抑制nesfatin-1诱导的PVN、VMH和TMH内t-MH的蓄积。第三脑室注射组胺可显著增加大鼠下丘脑PVN内nesfatin-1含量,但LH、VMH、TMN以及血浆内nesfatin-1水平无显著改变。免疫组化研究显示,PVN内有nesfatin-1和H1-R免疫反应阳性神经元,且部分神经元共存。结论:Nesfatin-1的抑食效应可能与下丘脑组胺信号通路介导。

Objective： To examine the interaction of nesfatin-1 in hypothalamus and histamine signaling pathways and the effect of nesfatin-1 in hypothalamus on the feeding behavior in rats. Methods： Third ventricle catheter, drug injection, immunohistochemistry,ELISA methods were used to observe the effects of FMH, CRH and TRH on the inhibition of feeding induced by nesfatin-1. In addition,the interaction of nesfatin-1 and histamine signaling pathways on the regulation of feeding. Results： Third ventricle nesfatin-1 had significantly reduced food intake in rats, while the feeding inhibition third of the third intraventricular injection of FMH, advance nesfatin-1 on rats reduced significantly, but the FMH itself does not affect night food intake in rats. The third ventricle injection of nesfatin-1, can significantly increase the pargyline induced t-MH accumulation in PVN, VMH, TMN; but the intraperitoneal injection of nesfatin-1 did not induce rat feeding change, t-MH accumulation also showed no significant changes. Third ventricle injection of alpha helix CRH serum can significantly reduce TRH nesfatin-1 feed inhibitory effect, while alpha helix CRH, TRH serum itself does not significantly affect food intake in rats. The third ventricle injection of nesfatin-1 can significantly increase the CRH and TRH levels in PVN, and nesfatin-1 can significantly increase the pargyline induced t-MH expression in PVN, VMH and TMN t-MH. Alpha helical CRH or anti-TRH serum can inhibit the nesfatin-1 induced accumulation of t-MH in PVN, VMH and TMH. Third ventricle injection of histamine can significantly increase the content of nesfatin-1 in PVN of hypothalamus, but the content of nesfatin-1 in LH and VMH,TMN and plasma had no significant changes. Immunohistochemical study showed that in PVN and H1-R nesfatin-1 immune response positive neurons, and part of the coexistence of neurons. Conclusions： The feeding inhibitory effect of nesfatin-1 may be related to the hypothalamus histamine signaling pathway mediated.