Gong Yanling, Liu Yang, Liu Fei, Wang Shasha, Jin Hong, Guo Feifei, Xu Luo
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China.
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China.
Brain Res. 2017 Mar 15;1659:29-40. doi: 10.1016/j.brainres.2017.01.004. Epub 2017 Jan 16.
Ghrelin can alleviate cancer chemotherapy-induced dyspepsia in rodents, though the neural mechanisms involved are not known. Therefore, ghrelin projections from the lateral hypothalamus (LH) and its involvement in the regulation of gastric motility in cisplatin-treated rats were investigated with a multi-disciplined approach. Retrograde tracing combined with fluoro-immunohistochemical staining were used to investigate ghrelin fiber projections arising from LH and projecting to nucleus tractus solitaries (NTS). Results revealed that ghrelin fibers originating in LH project to NTS. Expression of ghrelin and its receptor growth hormone secretagogue receptor (GHS-R1a) in LH and NTS were detected by Western Blot. 2days after cisplatin dosing, expression of ghrelin in LH decreased while GHS-R1a in both LH and NTS increased. In electrophysiological experiments, the effects of N-methyl-d-aspartate (NMDA) microinjection in LH on neuronal discharge of gastric distension-responsive neurons in NTS and gastric motility were assessed. NMDA in LH excited most of ghrelin-responsive gastric distension (GD)-sensitive neurons in NTS and promoted gastric motility. This effect was partially blocked by ghrelin antibody in NTS. Furthermore, the excitatory effects of NMDA in cisplatin-treated rats were weaker than those in saline-treated rats. Behaviorally, cisplatin induced a significant increase of kaolin consumption and decrease of food intake. These studies reveal a decreased expression of ghrelin in LH and up-regulation of GHS-R1a in LH and NTS, which are involved in the regulation of GD neuronal discharge in NTS and gastric motility.
胃饥饿素可减轻啮齿动物化疗引起的消化不良，但其涉及的神经机制尚不清楚。因此，采用多学科方法研究了来自下丘脑外侧区（LH）的胃饥饿素投射及其在顺铂处理大鼠胃动力调节中的作用。采用逆行追踪结合荧光免疫组织化学染色法，研究了起源于LH并投射到孤束核（NTS）的胃饥饿素纤维投射。结果显示，起源于LH的胃饥饿素纤维投射到NTS。通过蛋白质免疫印迹法检测LH和NTS中胃饥饿素及其受体生长激素促分泌素受体（GHS-R1a）的表达。顺铂给药2天后，LH中胃饥饿素的表达降低，而LH和NTS中GHS-R1a的表达增加。在电生理实验中，评估了向LH微量注射N-甲基-D-天冬氨酸（NMDA）对NTS中胃扩张反应性神经元放电及胃动力的影响。LH中的NMDA使NTS中大多数对胃饥饿素反应的胃扩张（GD）敏感神经元兴奋，并促进胃动力。NTS中的胃饥饿素抗体部分阻断了这一效应。此外，NMDA对顺铂处理大鼠的兴奋作用弱于生理盐水处理的大鼠。在行为学上，顺铂导致高岭土摄入量显著增加，食物摄入量减少。这些研究揭示了LH中胃饥饿素表达降低，以及LH和NTS中GHS-R1a上调，它们参与了NTS中GD神经元放电和胃动力的调节。
