多粘菌素B和杀菌/通透性增加蛋白对烫伤大鼠肠道细菌易位和肿瘤坏死因子-α基因表达的影响

Effects of antiendotoxin agents on bacterial translocation and tumor necrosis factorα mRNA expression in rats after thermal injury

目的：比较两种不同内毒素拮抗剂——多粘菌素Ｂ和杀菌／通透性增加蛋白（ＢＰＩ）对大鼠烫伤后肠道细菌易位和组织肿瘤坏死因子α（ＴＮＦα）基因表达的影响。方法：采用大鼠３５％体表面积Ⅲ度烫伤模型，动物随机分为正常对照组（８只）、烫伤组（２４只）、多粘菌素Ｂ治疗组（７只）和ＢＰＩ治疗组（６只）。结果：大鼠烫伤后肠道细菌易位率明显上升，伤后８小时细菌易位率达３７．１％，与正常对照组比较差异显著（Ｐ＜０．０１）；细菌易位率最高的器官是肠系膜淋巴结，不同器官易位细菌量无显著性差异；给予烫伤大鼠多粘菌素Ｂ和ＢＰＩ治疗均可不同程度地降低细菌易位率，其细菌易位率分别降至烫伤８小时组的６１．７％和５３．９％；ＢＰＩ比多粘菌素Ｂ更为有效地降低肠、肾等组织ＴＮＦαｍＲＮＡ表达水平（Ｐ均＜０．０１）。结论：多粘菌素Ｂ和ＢＰＩ均可降低大鼠烫伤后肠道细菌易位的发生；ＢＰＩ较多粘菌素Ｂ能更有效地抑制多种组织ＴＮＦαｍＲＮＡ表达。因此，烧伤早期应用ＢＰＩ治疗对抑制创伤后机体过度炎症反应具有重要意义。

Objective:To evaluate the effects of antiendotoxin agents on bacterial translocation and tumor necrosis factorα(TNFα) gene expression following thermal injury.Methods:45 male Wistar rats were subjected to a 35% total body surface area full thickness thermal injury,and randomly divided into 4 groups as follows:①normal controls;②thermal injury group,which was further divided into postburn 2,8,24 hours groups,respectively;③polymyxin B treatment group;④recombinant bactericidal/permeabilityincreasing protein (BPI) treatment group.Results:It was found that incidences of bacterial translocation were significantly increased at various time points,being 37 1% at 8 hours postburn ( P <0 01).Translocating organisms were predominately detected in mesenteric lymph nodes,and the amount of bacteria was not significantly different in various organs.Treatment with BPI and polymyxin B could markedly diminish total incidence of bacterial translocation,and higher inhibitory effect on TNFα mRNA in intestine,kidneys was found in BPI group compared to polymyxin B group (both P <0 01).Conclusions:BPI and polymyxin B can reduce the incidence of bacterial translocation after burns.Early use of BPI has inhibitory effect on TNFα induction,showing that BPI might be a new therapeutic agent against systemic inflammatory response associated with endogenous infection following acute burns.