Ghrelin prevents lethality in a rat endotoxemic model through central effects on the vagal pathway and adenosine A2B signaling : Brain ghrelin and anti-septic action.

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Sho Igarashi, Tsukasa Nozu, Masatomo Ishioh, Takuya Funayama, Chihiro Sumi, Takeshi Saito, Yasumichi Toki, Mayumi Hatayama, Masayo Yamamoto, Motohiro Shindo, Hiroki Tanabe, Toshikatsu Okumura
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Abstract

Accumulating evidence suggest that ghrelin plays a role as an antiseptic peptide. The present study aimed to clarify whether the brain may be implicated ghrelin's antiseptic action. We examined the effect of brain ghrelin on survival in a novel endotoxemic model achieved by treating rats with lipopolysaccharide (LPS) and colchicine. The observation of survival stopped three days after chemicals' injection or at death. Intracisternal ghrelin dose-dependently reduced lethality in the endotoxemic model; meanwhile, neither intraperitoneal injection of ghrelin nor intracisternal des-acyl-ghrelin injection affected the mortality rate. The brain ghrelin-induced lethality reduction was significantly blocked by surgical vagotomy. Moreover, intracisternal injection of a ghrelin receptor antagonist blocked the improved survival achieved by intracisternal ghrelin injection or intravenous 2-deoxy-d-glucose administration. Intracisternal injection of an adenosine A2B receptor agonist reduced the lethality and the ghrelin-induced improvement of survival was blocked by adenosine A2B receptor antagonist. I addition, intracisternal ghrelin significantly blocked the colonic hyperpermeability produced by LPS and colchicine. These results suggest that ghrelin acts centrally to reduce endotoxemic lethality. Accordingly, activation of the vagal pathway and adenosine A2B receptors in the brain may be implicated in the ghrelin-induced increased survival. Since the efferent vagus nerve mediates anti-inflammatory mechanisms, we speculate that the vagal cholinergic anti-inflammatory pathway is implicated in the decreased septic lethality caused by brain ghrelin.

Abstract Image

在大鼠内毒素模型中,胃饥饿素通过迷走神经通路和腺苷A2B信号的中枢作用来预防致死性:脑胃饥饿素和抗菌作用。
越来越多的证据表明胃饥饿素起着抗菌肽的作用。目前的研究旨在澄清大脑是否与胃饥饿素的杀菌作用有关。我们在一种新的内毒素模型中研究了脑饥饿素对大鼠生存的影响,这种内毒素模型是用脂多糖和秋水仙碱治疗的。注射化学物质3天后或死亡时停止生存观察。内毒素模型中胃促生长素剂量依赖性降低致死率;同时,腹腔注射胃饥饿素和腹腔注射去酰基胃饥饿素对死亡率均无影响。迷走神经切开术明显阻断了胃饥饿素诱导的脑致死性降低。此外,肠内注射胃饥饿素受体拮抗剂阻断了肠内注射胃饥饿素或静脉注射2-脱氧-d-葡萄糖所改善的生存。脑内注射腺苷A2B受体激动剂可降低致死性,腺苷A2B受体拮抗剂可阻断胃饥饿素诱导的生存改善。肠内胃饥饿素显著阻断LPS和秋水仙碱引起的结肠高通透性。这些结果表明,胃饥饿素在降低内毒素致死性方面起主要作用。因此,脑内迷走神经通路和腺苷A2B受体的激活可能与胃饥饿素诱导的存活增加有关。由于传出迷走神经介导抗炎机制,我们推测迷走神经胆碱能抗炎途径与脑饥饿素引起的脓毒性死亡率降低有关。
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来源期刊
Journal of physiology and biochemistry
Journal of physiology and biochemistry 生物-生化与分子生物学
CiteScore
6.60
自引率
0.00%
发文量
86
审稿时长
6-12 weeks
期刊介绍: The Journal of Physiology and Biochemistry publishes original research articles and reviews describing relevant new observations on molecular, biochemical and cellular mechanisms involved in human physiology. All areas of the physiology are covered. Special emphasis is placed on the integration of those levels in the whole-organism. The Journal of Physiology and Biochemistry also welcomes articles on molecular nutrition and metabolism studies, and works related to the genomic or proteomic bases of the physiological functions. Descriptive manuscripts about physiological/biochemical processes or clinical manuscripts will not be considered. The journal will not accept manuscripts testing effects of animal or plant extracts.
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