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.

大肠杆菌O-157致肾损害与脂多糖（LPS）和verotoxin-2（VT-2）有关。然而，每种药物注射后的病理生理学特征并未得到充分评价。本研究就是为了解决这一问题。LPS对大鼠的时间毒性于9：00或21：00给Wistar大鼠静脉注射LPS（5 mg/kg），观察其对大鼠脏器的损伤作用。21：00试验的器官损害程度明显大于9：00试验。在21：00试验中，血清白细胞介素-6（IL-6）（一种炎性细胞因子）的升高更大，其在器官中的合成也更增强。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.抗中性粒细胞抗体对维生素T_2诱导的小鼠器官损伤的预防作用在给予维生素T_2（100 ng）后的0和24 h，给C57 BL/6小鼠腹腔注射维生素T_2（100 ng），同时给予抗中性粒细胞抗体和不给予抗中性粒细胞抗体。单独注射VT_2后，血浆中性粒细胞明显升高，所有动物均于注射后5天内死亡。在具有抗中性粒细胞抗体的小鼠中，死亡率显著降低。提示中性粒细胞在VT_2引起的器官损害中起一定作用。