Intracellular pathways of shock induced by gram-positive bacteria

革兰氏阳性菌诱导休克的细胞内途径

• 批准号: 11671503
• 负责人: OGURA Shinji
• 金额: $ 2.3万
• 依托单位: KAGWA MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671503/
• 关键词: Gram-positive bacteria; shock; sepsis; anti-thrombin III; tyrosine kinase; cytokine; GBS; antithrombin III; 敗血症性ショック; Tyrosine; Shock; Seplic Shock; LPS

To clear the mechanisms of beneficial effect of antithrombin III (ATIII) on septic shock, we have investigated rat shock model induced by cecal ligation puncture (CLP). Animals subjected to CLP exhibited severe shock with a mean survival time of 15.6 hours, and finally all animals expired. ATIII treated animals simultaneously with CLP significantly prolonged survival and 50% of the rats survived. CLP increased serum IL-6 concentration remarkably at 2, 4, 8 hours after the start of experiment. ATIII significantly decreased the cytokine production. To investigate the direct cellular effects of ATIII, rat peritoneal macrophages were collected and harvested as previously described. Adherent cells were stimulated with either Endotoxin (LPS) or heat killed group B streptococcus (GBS) in the presence or absence of ATIII.IL-6 production from macrophages was activated with LPS and GBS, whereas ATIII inhibited the increase. IL-2 production was slightly increased from the control but ATIII did not affect the production. These results indicate that ATIII may have beneficial effects on rat shock, possibly by blocking inflammatory cytokine production directly.

为探讨抗凝血酶III（ATIII）对感染性休克的治疗作用机制，本研究采用盲肠结扎穿孔（CLP）法建立大鼠感染性休克模型。遭受CLP的动物表现出严重休克，平均生存时间为15.6小时，最终所有动物均死亡。ATIII治疗的动物同时CLP显着延长生存和50%的大鼠存活。CLP组在实验开始后2、4、8h血清IL-6浓度显著升高。ATIII显著降低细胞因子的产生。为了研究ATIII的直接细胞效应，如前所述收集和收获大鼠腹腔巨噬细胞。用内毒素（LPS）或热灭活的B族链球菌（GBS）刺激贴壁细胞，在有或无ATIII的情况下，LPS和GBS激活巨噬细胞产生IL-6，而ATIII抑制巨噬细胞产生IL-6的增加。IL-2的产生比对照略有增加，但ATIII不影响产生。这些结果表明ATIII可能对大鼠休克具有有益作用，可能是通过直接阻断炎性细胞因子的产生。

项目成果

Ogura S.: "Effects of human antithrombin III or rat shock"Proceeding of 5th world congress on traumae, shock. 147-152 (2000)

Ogura S.：“人类抗凝血酶 III 或大鼠休克的影响”第五届世界创伤、休克大会记录。

Ogara S.: "Protective Effect of Tyrphostin AG-556 on Shock Induced by."SHOCK. 12. 105-110 (1999)

Ogara S.：“酪氨酸磷酸酶 AG-556 对由休克引起的休克的保护作用。”休克。

Ogara S.: "Effects of human antithrombin III or rat cecal ligation puncture shock"SHOCK. 11. 49 (1999)

Ogara S.：“人抗凝血酶 III 或大鼠盲肠结扎穿刺休克的影响”震惊。

Ogura S: "Protective Effect of Tyrphostin AG-556 ** Shock Indeced by **doto** or Gram Positive Bacteria"Shock. 12(2). 105-110 (1999)

Ogura S：“酪氨酸磷酸酶 AG-556 ** 由 **doto** 或革兰氏阳性细菌引起的休克的保护作用”休克。

小倉真治: "ラットショックモデルにおけるAntithrombin III(ATIII)の有効性の機序"日本救急医学会誌. 11. 545 (2000)

Shinji Ogura：“抗凝血酶 III (ATIII) 在大鼠休克模型中的有效性机制”日本急救医学会杂志 11. 545 (2000)。