Guo Feifei, Xu Luo, Gao Shengli, Sun Xiangrong, Zhang Nana, Gong Yanling
Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, 266021, Shandong, China.
Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, 266021, Shandong, China.
Neurosci Res. 2019 Jun;143:53-60. doi: 10.1016/j.neures.2018.06.001. Epub 2018 Jun 4.
The most common side effects of the cancer chemotherapy drug cisplatin are nausea and vomiting. These effects are heavily influenced by orexigenic and anorexigenic peptides. We explored the effects of orexin-A on the cisplatin-treated rats and a possible mechanism for its effects on cisplatin-induced side effects. Quantitative real-time PCR was used to measure the change of prepro-orexin mRNA in the hypothalamus following cisplatin treatment. The effect of orexin-A and cisplatin on the firing rate of arcuate nucleus neurons was recorded. The effect of administration of orexin-A and a neuropeptide Y1 receptor antagonist to the arcuate nucleus on food intake, pica, and gastric motility on cisplatin treated rats were also measured. The relative expression of prepro-orexin mRNA in the hypothalamus was reduced by cisplatin. Exogenous orexin-A altered cisplatin-induced changes to the neuronal firing of gastric distension-responsive neurons, alleviated the cisplatin-induced anorexia, pica and improves the weakened gastric motility in the arcuate nucleus of rats. These effects could be partially blocked by intracerebroventricular injection (i.c.v.) of a neuropeptide Y1 receptor antagonist. These results suggest that orexin-A signaling ameliorates the gastric disorder induced by cisplatin in rats, and may act through neuropeptide Y neurons in the arcuate nucleus.
癌症化疗药物顺铂最常见的副作用是恶心和呕吐。这些副作用受到促食欲肽和抑食欲肽的严重影响。我们探究了食欲素A对顺铂处理的大鼠的影响及其对顺铂诱导的副作用的作用机制。采用定量实时聚合酶链反应来测量顺铂处理后下丘脑前食欲素原信使核糖核酸的变化。记录了食欲素A和顺铂对弓状核神经元放电频率的影响。还测量了向弓状核注射食欲素A和一种神经肽Y1受体拮抗剂对顺铂处理大鼠的食物摄入量、异食癖和胃动力的影响。顺铂降低了下丘脑前食欲素原信使核糖核酸的相对表达。外源性食欲素A改变了顺铂诱导的胃扩张反应性神经元的神经元放电变化，减轻了顺铂诱导的厌食、异食癖，并改善了大鼠弓状核中减弱的胃动力。这些作用可通过脑室内注射神经肽Y1受体拮抗剂部分阻断。这些结果表明，食欲素A信号传导改善了顺铂诱导的大鼠胃部紊乱，可能通过弓状核中的神经肽Y神经元起作用。
