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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 investigate the interaction between hypothalamic nesfatin-1 and histamine signaling pathway and their effects on feeding. Methods: The effects of fluoromethyl histidine (FMH), α-helical corticotropin-releasing hormone (CRH) and thyrotropin-releasing hormone (TRH) were observed by the third ventricular catheterization, drug injection, immunohistochemistry and ELISA. ) On Nesfatin-1-induced inhibition of feeding and the interaction between Nesfatin-1 and histamine signaling regulates feeding mechanism. Results: The third ventricle injection of nesfatin-1 can significantly reduce the rat food intake, while the third ventricle pre-injection of FMH, nesfatin-1 inhibit the feeding effect was significantly reduced, but FMH itself does not affect the nighttime food intake. The nesfatin-1 injection into the third ventricle significantly increased the accumulation of t-MH in the PVN, VMH and TMN of the superior ventricles of rats. However, intraperitoneal injection of nesfatin-1 did not induce food intake Changes, t-MH accumulation also did not change significantly. The third ventricle injection of α-helix CRH or anti-TRH serum can significantly reduce nesfatin-1 inhibitory effect, and α-helix CRH, anti-TRH serum itself does not significantly affect the food intake. Nesfatin-1 injection into the third ventricle significantly increased the levels of CRH and TRH in PVN of hypothalamus, and nesfatin-1 significantly increased the expression of t-MH in PVN, VMH and TMN induced by orphanin, while α-helix CRH or anti-TRH Serum significantly inhibited nesfatin-1-induced accumulation of t-MH in PVN, VMH and TMH. Histamine injection into the third ventricle significantly increased the content of nesfatin-1 in the hypothalamus PVN, but the levels of LH, VMH, TMN and nesfatin-1 in plasma did not change significantly. Immunohistochemical studies showed that there are nesfatin-1 and H1-R immunoreactive neurons in PVN, and some neurons coexist. Conclusion: The inhibitory effect of Nesfatin-1 may be mediated by the hypothalamic histamine signaling pathway.