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閲覧数:181
ID 20220325_K574
アイテムタイプ Article
このアイテムを表示する
本文 K574 Igarashi Sho_TD.pdf
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Size : 4.4 MB
Last updated : Aug 19, 2022
Downloads : 234

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タイトル Centrally administered orexin prevents lipopolysaccharide and colchicine induced lethality via the vagal cholinergic pathway in a sepsis model in rats (オレキシン中枢投与は,リポポリサッカライドとコルヒチンによるラット敗血症死をコリン作動性迷走神経路を介して改善する)
著者
五十嵐, 将 (Igarashi, Sho)
上位タイトル
Biochemical Pharmacology No.182  (2020. 12) ,p.114262-
識別番号
ISSN
0006-2952
DOI 10.1016/j.bcp.2020.114262
その他
PMID:33035510
博士論文情報
学位授与番号 10107A574
学位授与年月日 2022-03-25
学位名 博士(医学)
学位授与機関 旭川医科大学
抄録 Orexins are neuropeptides implicated in several physiological functions. Accumulating findings suggest a relationship between orexin and sepsis. A recent study demonstrated that orexin acts centrally to improve conditions in sepsis. The present study aims to clarify the precise mechanisms by which central orexin could induce a protective action against septic conditions. We established a new septic model by treating rats with lipopolysaccharide (LPS) and colchicine and used this to examine the effect of brain orexin on survival. Observation of survival was stopped three days after the chemicals injection or at death. We established a lethal model (rats died within 24 h) by injecting subcutaneously a combination of 1 mg/kg LPS and 1 mg/kg colchicine. A Toll-like receptor 4 (TLR4) inhibitor completely blocked lethality, suggesting a vital role of LPS-TLR4 signaling in the process. Intracisternal orexin-A dose-dependently reduced lethality in the sepsis model while neither intracisternal orexin-B nor intraperitoneal orexin-A changed the mortality rate. Vagal stimulation with carbachol or 2-deoxy-D-glucose improved survival and atropine potently blocked the protection by carbachol or 2-deoxy-D-glucose. The orexin-A-induced reduction of lethality was significantly blocked by atropine or surgical vagotomy. Intracisternal injection of an OX1 receptor antagonist blocked the improvement of survival by intracisternal injection of orexin-A, carbachol, or 2-deoxy-D-glucose. These results suggest that orexin acts centrally to reduce the lethality in our septic model treated (LPS and colchicine). Activation of the vagal cholinergic pathway may mediate the action of orexin, and the OX1 receptor in the brain might play a role in the process. Since the efferent vagus nerve mediates anti-inflammatory mechanisms, we speculate that the vagal cholinergic anti-inflammatory pathway is implicated in the mechanisms of septic lethality reduction by brain orexin.
キーワード
Central nervous system
Colchicine
Lipopolysaccharide
Orexin
Sepsis
Vagus
言語
eng
資源タイプ application/pdf
ジャンル Thesis or Dissertation
著者版フラグ ETD
Index
/ Public
/ Public / 学位論文
/ Public / 学位論文 / 博士論文2020.3~
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