Early detection of postoperative sepsis and organ dysfunction using cDNA micro-array and therapeutic strategy for these complications by anti-TLR antibody.

使用 cDNA 微阵列早期检测术后败血症和器官功能障碍，并通过抗 TLR 抗体治疗这些并发症。

• 批准号: 17591374
• 负责人: KIMURA Fumio
• 金额: $ 2.05万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591374/
• 关键词: organ dysfunction; postoperative sepsis; cDNA micro-array; anti-TLR antibody; GATA3; T-bet; sC30

Background/Objectives : Aggressive hepatobiliary pancreatic surgery has been associated with high complication rates. Early detection of postoperative sepsis and organ dysfunction using cDNA micro-array and transcription-polymerase chain reaction (RT-PCR) was evaluated in patients undergoing hepatobiliary pancreatic surgery. Furthermore, therapeutic effects of anti-TLR2, 4 antibodies on these complications were determined in animal models with peritoneal sepsis or obstructive jaundice.Methods : Plasma concentrations of interleukin (IL)-6, IL-10, soluble lymphocyte activation gene (sLAG) -3, and soluble CD30 (sCD30) were determined by ELISA perioperatively in consecutive 56 patients who underwent hepatobiliary pancreatic surgery. Gene expression in PBMCs was analysed by cDNA micro-array, and expression levels of T-bet, GATA-3, TLR2, and TLR4 mRNA in PBMCs were confirmed by reverse RT-PCR.Effects of anti-TLR2, 4 antibodies on sepsis were determined in animal models with peritoneal sepsis … More or obstructive jaundice.Results : Of the 56 patients, 30 patients had postoperative infection. Postoperative plasma levels of IL-6 and IL-10 were significantly higher in patients with postoperative infection than in those without infection (p<0.05). sCD30 levels were significantly higher preoperatively, and remained higher by postoperative day 7 in patients with postoperative infection (p<0.05). sLAG-3 levels were not significantly different between two groups. GATA-3 mRNA expression level was significantly higher preoperatively, and remained higher by postoperative day 7 in patients with postoperative infection (p<0.05). T-bet mRNA expression level was significantly higher on postoperative days 3, 7, and 14 in patients with postoperative infection (p<0.05). TLR2 and TLR4 mRNA expression levels were significantly higher on postoperative day 3 in patients with postoperative infection (p< 0.05). Preoperative expression levels of GATA-3 mRNA correlated significantly with those of TLR2 and TLR4 mRNA (p<0.05). Anti-TLR2, 4 antibodies were not effective in animal models with peritoneal sepsis or obstructive jaundice.Conclusions : These results suggest that preoperative Th1/Th2 balance shifts toward Th2 dominance in patients with postoperative infection, and preoperative expression levels of circulating sCD30 and GATA3 mRNA in PBMCs are the novel markers predicting postoperative sepsis and organ dysfunction. Less

背景/目的：侵袭性肝胆胰手术与高并发症发生率相关。应用cDNA微阵列和转录聚合酶链反应（RT-PCR）对肝胆胰手术患者术后脓毒症和器官功能障碍的早期检测进行了评价。方法：采用酶联免疫吸附试验（ELISA）检测56例肝胆胰手术患者围手术期血浆白细胞介素（IL）-6、IL-10、可溶性淋巴细胞活化基因（sLAG）-3和可溶性CD 30（sCD 30）水平。采用cDNA微阵列技术检测PBMCs基因表达，逆转录-聚合酶链反应（RT-PCR）检测T-bet、加塔-3、TLR 2、TLR 4 mRNA的表达水平，观察抗TLR 2、4抗体对腹腔感染的影响 ...更多信息 结果：56例患者中，30例发生术后感染。术后感染组术后血浆IL-6、IL-10水平明显高于无感染组（P<0.05）。术前sCD 30水平显著升高，术后感染患者术后7天sCD 30水平仍较高（p<0.05）。sLAG-3水平在两组之间无显著差异。术后感染组加塔-3 mRNA表达水平在术前明显升高，术后7 d仍高于术前（p<0.05）。术后感染组术后3、7、14 d T-bet mRNA表达水平明显高于对照组（P<0.05）。术后感染组TLR 2、TLR 4 mRNA表达水平在术后第3天明显高于术后感染组（p< 0.05）。术前加塔-3 mRNA表达水平与TLR 2、TLR 4 mRNA表达水平显著相关（p<0.05）。结论：腹腔感染患者术前Th 1/Th 2平衡向Th 2优势方向偏移，术前外周血单个核细胞sCD 30和GATA 3 mRNA表达水平是预测术后脓毒症和器官功能障碍的新指标。少

项目成果

Circulating cytokines, chemokines, and stress hormones are increased in patients with organ dysfunction following liver resection

• DOI: 10.1016/j.jss.2005.10.025
• 发表时间: 2006-06-15
• 期刊: JOURNAL OF SURGICAL RESEARCH
• 影响因子: 2.2
• 作者: Kimura, F;Shimizu, H;Miyazaki, M
• 通讯作者: Miyazaki, M