Study on Escherichia coli O-157-induced renal damage

大肠杆菌O-157所致肾损伤的研究

• 批准号: 11672273
• 负责人: FUJIMURA Akio
• 金额: $ 2.3万
• 依托单位: Jichi 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 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672273/
• 关键词: E-coli O157; verotoxin; lipopoly saccharide; renal damage; neutrophil; O-157; 抗好中球抗体; 腎障害; IL6; 時間薬理

Lipopolysaccharide (LPS) and verotoxin-2 (VT2) are involved in the Escherichia coli O-157-induced renal damage. However, pathophysiologic profiles are not fully evaluated after an injection of each agent. This study was undertaken to address this issue.1. Chronotoxicity of LPS in ratsLPS (5 mg/kg) was injected intravenously to Wistar rats at 9:00 or 21:00, and organ damages were evaluated. The degree of organ damages in the 21:00 trial were significantly greater than those in the 9:00 trial. The elevation in serum interleukin-6 (IL-6), an inflammatory cytokine, was greater and its synthesis in organs was more enhanced in the 21:00 trial. These data indicate that the toxicity of LPS depends on its dosing time, probably through the time-dependent difference in the IL-6 response.2. Preventive effect of anti-neutrophil antibody against the VT_2-induced organ damage in mice.VT_2 (100 ng) was injected intraperitoneally to C57BL/6 mice with and without the co-administration of anti-neutrophil mouse antibody at 0 and 24 hours following VT_2. After the injection of VT_2 alone, plasma neutrophil remarkably elevated and all animals died within 5 days after the VT_2 injection. Death rate was significantly reduced in mice with the anti-neutrophil antibody. These data suggest that neutrophil plays some role in the VT_2-induced organ damage.

脂多糖 (LPS) 和 verotoxin-2 (VT2) 参与大肠杆菌 O-157 诱导的肾损伤。然而，注射每种药物后并未完全评估病理生理学特征。本研究就是为了解决这个问题而进行的。 1． LPS对大鼠的时间毒性Wistar大鼠于9:00或21:00静脉注射LPS(5mg/kg)，评价器官损伤情况。 21:00试验的器官损伤程度明显大于9:00试验。在 21:00 的试验中，血清白细胞介素 6 (IL-6)（一种炎症细胞因子）的升高幅度更大，并且其在器官中的合成也更多增强。这些数据表明LPS的毒性取决于其给药时间，可能是通过IL-6反应的时间依赖性差异。2．抗中性粒细胞抗体对 VT_2 诱导的小鼠器官损伤的预防作用。在 VT_2 后 0 小时和 24 小时，将 VT_2 (100 ng) 腹腔注射给 C57BL/6 小鼠，并联合或不联合施用抗中性粒细胞小鼠抗体。单独注射VT_2后，血浆中性粒细胞显着升高，所有动物在注射VT_2后5天内死亡。使用抗中性粒细胞抗体的小鼠的死亡率显着降低。这些数据表明中性粒细胞在 VT_2 诱导的器官损伤中发挥一定作用。