下丘脑Nesfatin-1抑食效应及机制研究

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。

Nesfatin-1 in the Hypothalamus Antifeedant Effect and MechanismStudy

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.Conclusion:The feeding inhibitory effect of nesfatin-1 may be related to the hypothalamus histamine signaling pathway mediated.