敗血症における自律神経系活動のcytokine動態への関与と治療法の確立

脓毒症中自主神经系统活性参与细胞因子动力学及治疗方法的建立

• 批准号: 22592009
• 负责人: 仲村 将高
• 金额: $ 2.58万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22592009/
• 关键词: 敗血症; Inflammatory reflex; Cytokine theory; beta-blocker; HRV解析; severe sepsis/septic shock; cecal ligation puncture; cholinergic anti-inflammatory pathway; cytokine theory of disease; heart rate variability; immunomodulation

Severe sepsis/septic shockにおけるcytokine cascade活性化と病態との関係で,我々はこれまでに主に臨床研究に取り組み,平成20年度においては第23回日本Shock学会総会,第36回日本集中治療医学会学術集会にその成果を発表した.一方,近年severe sepsis/septic shockの病態生理におけるcytokine productionの制御系として自律神経系を介した抗炎症反応系(cholinergic anti-inflammatory pathway)の存在が提唱されるようになり,我々はinflammatory flexの評価法とその治療法を解明する事を目的に動物実験に基づいた本研究を開始した.オスSDラットを用い,cecal ligation puncture(CLP)モデルを作成したのち,末梢性副交感神経刺激薬のジスチグミンや,中枢性副交感神経刺激薬のトロピセトロンを投与し,それらを投与していないCLPモデル群とで,サイトカイン動態を検討した.その結果,CLPモデル群に比較し,CLP下でジスチグミンや,トロピセトロンを投与した群では,TNF-alpha,IL-6などの炎症性サイトカインの産生が有意に抑制された.これらの事から,自律神経系のうち副交感神経を刺激する事によって敗血症における炎症性サイトカインの過剰産生が制御されうる事が示唆された.本研究の成果は,Int Immunopharmacol 11;2073-8,2011,Cytokine 57;238-44,2012にそれざれ投稿し受理された.今後,交感神経系に作用する薬剤などを用いてこれらの自律神経系とcytokine production系について検討を重ねる方針である.

Severe sepsis/septic shock has a history of cytokine cascade activation and disease, and we are in charge of bed research. Pingcheng returned to the 23rd meeting of the Shock Society of Japan in the year of 20, and the 36th to Japan to focus on the academic meeting of the Medical Association. On the one hand, in recent years, the severe sepsis/septic shock disease physiology system, the cytokine production system, the self-discipline system, the anti-inflammatory reaction system (cholinergic anti-inflammatory pathway), the anti-inflammatory reaction system (cholinergic anti-inflammatory pathway), the anti-inflammatory system, the anti-inflammatory system and the anti-inflammatory system. SD (CLP) parasympathetic stimuli, central parasympathetic stimuli, peripheral parasympathetic stimuli, central parasympathetic stimuli, central parasympathetic stimuli, peripheral parasympathetic stimuli, central parasympathetic stimuli, peripheral parasympathetic stimuli, central parasympathetic stimuli, central parasympathetic stimuli The results showed that the results of TNF-alpha,IL-6 test showed that there were significant differences between the two groups in terms of CLP, CLP and CLP. Self-discipline, parasympathetic stimulation, parasympathetic syndrome, inflammatory disease, inflammation, control, prevention and treatment. In this study, Int Immunopharmacol 11 ~ (th), 2011 ~ (th) Cytokine 57 ~ (th) ~ (th), 238-44 ~ (th), 2011 ~ (th) From now on, the sympathetic god is in the role of self-discipline and self-discipline. In the future, the sympathetic god is responsible for the cytokine production system.

项目成果

Effects of a peripheral cholinesterase inhibitor on cytokine production and autonomic nervous activity in a rat model of sepsis.

• DOI: 10.1016/j.cyto.2011.11.003
• 发表时间: 2012-02
• 期刊: Cytokine
• 影响因子: 3.8
• 作者: D. Setoguchi;Henry Yatsuki;Tomohito Sadahiro;Masataka Nakamura;Y. Hirayama;Eizo Watanabe;Y. Tateishi;S. Oda

Experimental examination of anti-inflammatory effects of 5-HT receptor antagonist tropisetron and concomitant effects on autonomic nervous function in a rat sepsis model

5-HT受体拮抗剂托烷司琼抗炎作用及其对败血症模型大鼠自主神经功能的实验研究

• 发表时间: 2011
• 期刊: Int Immunopharmacol
• 影响因子: 5.6
• 作者: Setoguchi D;Nakamura M;Oda S;et al.
• 通讯作者: et al.