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

背景/目的：积极的肝胆胰术后并发症发生率较高。应用基因芯片和转录-聚合酶链式反应(RT-PCR)对肝胆胰腺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估。方法：采用酶联免疫吸附试验检测56例肝胆胰腺手术患者围手术期血浆IL-6、IL-10、可溶性淋巴细胞活化基因(SGRAG)-3、可溶性CD30的浓度。逆转录-聚合酶链式反应(RT-…)检测T-bet、GATA-3、TLR2、TLR4mRNA的表达水平，观察抗TLR2、TLR4抗体对脓毒症动物模型的治疗作用结果：56例患者中，术后感染30例。术后感染组血浆IL-6、IL-10水平显著高于未感染组(p&lt；0.05)。在术后感染的患者中，sCD30水平在手术前显著升高，并在术后第7天保持较高水平(p&lt；0.05)。两组间的矿渣蛋白-3水平无显著差异。在术后感染的患者中，GATA-3mRNA的表达水平在术前显著升高，并在术后第7天保持较高水平(p&lt；0.05)。术后感染组T-bet基因表达在术后第3、7、14天显著高于对照组(p&lt；0.05)。术后感染患者术后第3天TLR2和TLR4mRNA表达水平显著高于对照组(p&lt；0.05)。GATA-3mRNA表达水平与TLR2、TLR4mRNA表达水平呈显著正相关(p&lt；0.05)。结论：术后感染患者术前Th1/Th2平衡向Th2优势偏移，PBMC中循环sCD30和GATA3mRNA的表达水平可作为预测术后脓毒症和器官功能障碍的新指标。较少

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