Molecular and cellular basis of septic shock : Involvement of anandamide and HMG-1

感染性休克的分子和细胞基础：anandamide 和 HMG-1 的参与

• 批准号: 13470324
• 负责人: MARUYAMA Ikuro
• 金额: $ 1.92万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470324/
• 关键词: HMG-1; anandamide; endocannabinoids; 2-arachidonylflyceorol; septic shock; polymyxin B; アナンダマイド; エンドトキシンショック; ポリミキシンB; アポトーシス

Bacterial septicemia results hypotensive shock in severe cases. Various mediators have been proposed as causative factors in this hypotensive shock. These include inflammatory cytokines, PAF, NO and so on. However the inhibitors or antibodies against the mediators failed to improve hypotensive shock in clinical studies. Thus the other mediators may exist to cause septic shock.In the present investigations, we identified that endocannabinoids, anandamide and 2-arachidonylglycerol which axe produced and secreted from stimulated macrophages and platelets induce hypotension, and act as an early hypotensive mediators. We also identified that polymyxin B selectively binds these endocannabinoids. Hemo-perfusion through polymyxin B-coated biomembrane column efficiently removed the circulating endocannabinoids and results rapid improvement of the hypotension.Then we investigated the role of HMG-1 on the pathogenesis of septic shock, and showed that HMG-1 may act as a late phase mediator in septic shock.

细菌败血症会导致严重病例的降压冲击。在这种降压冲击中，已经提出了各种介体作为致病因素。这些包括炎症细胞因子，PAF，否等等。但是，针对介体的抑制剂或抗体在临床研究中无法改善降压冲击。因此，其他介体可能会引起败血性休克。在本研究中，我们确定内源性大麻素，anandamide和2-芳基甘油甘油，AX产生并从刺激的巨噬细胞和血小板中产生和分泌，可诱导高血压，并起早期降低性降低性介体。我们还鉴定出多粘蛋白B有选择地结合这些内源性大麻素。通过多聚酸性B涂的生物膜柱的血液灌注有效地去除了循环的内源性大麻素，并结果迅速改善了低血压。然后，我们研究了HMG-1在败血性休克的发病机理上的作用，并表明HMG-1可能在败血症后期休克中起到后期介质的作用。

项目成果

Kazuyo Yamaji, Krishna Pada Sarker, Koichi Kawahara, Satoshi Iino, Munekazu Yamakuchi, Kazuhiro Abeyama, Teruto Hashiguchi, Ikuro Maruyama: "Anandamide induces apotosis in human endothelial cells : its regulation system and clinical implication."Thromb Ha

Kazuyo Yamaji、Krishna Pada Sarker、Koichi Kawahara、Satoshi Iino、Munekazu Yamakuchi、Kazuhiro Abeyama、Teruto Hashiguchi、Ikuro Maruyama：“Anandamide 诱导人内皮细胞凋亡：其调节系统和临床意义。”血栓 Ha

Niiyama, T., Higuchi, I., Suehara, M.et al.: "Electron microscopic abnormalities of skeletal muscle in patients with collagen VI deficiency in Ullrich's disease"Acta Neuropathol.. 104. 67-71 (2002)

Niiyama, T.、Higuchi, I.、Suehara, M.等：“乌尔里希病中胶原 VI 缺乏症患者骨骼肌的电子显微镜异常”Acta Neuropathol.. 104. 67-71 (2002)

Kawabata H., Maruyama.I.: "Possible role of transcriptional coactivator P/CAF and nuclear acetylation in calcium-induced kerationcyte differentiation"J Biol Chem. 277・10. 8099-8105 (2002)

Kawabata H.，Maruyama.I.：“转录共激活因子 P/CAF 和核乙酰化在钙诱导的角质细胞分化中的可能作用”J Biol Chem. 277・10 (2002)。

Noboru Taniguchi, Ko-ichi Kawahara, Kazunori Yone, Teruto Hashiguchi, Munekazu Yamakuchi, Masamichi Goto, Keiichi Inoue, Shingo Yamada, Kosei Ijiri, Shunji Matsunaga, Toshihiro Nakajima, Setsuro Komiya, and Ikuro Maruyama: "High Mobility Group Box Chromos

Noboru Taniguchi、Ko-ichi Kawahara、Kazunori Yone、Teruto Hashiguchi、Munekazu Yamakuchi、Munekazu Goto、Keiichi Inoue、Shingo Yamada、Kosei Ijiri、Shunji Matsunaga、Toshihiro Nakajima、Setsuro Komiya 和 Ikuro Maruyama：“高机动组 Box Chromos”

Yamaji, K., Krishna P.Sarker, Hashiguchi, T., et al.: "Endocannabinoids induces apoptotic cell death in cultured endothelial cells"Thromb. Haemost. (In press).

Yamaji, K.、Krishna P.Sarker、Hashiguchi, T. 等人：“内源性大麻素在培养的内皮细胞中诱导细胞凋亡”血栓。