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目的:探讨脂多糖结合蛋白(LBP)在严重创伤后肠源性内毒素血症诱发多器官损害中的作用及杀菌/通透性增加蛋白(BPI)的防治效应。方法:采用大鼠重度失血性休克(30~35mmHg,180min)、35%Ⅲ°烫伤模型,观察应用重组BPI(rBPI21)对血浆内毒素含量,肺、肝、肠、肾等组织LBPmRNA表达,多器官病理改变及动物存活率的影响。结果:给予rBPI21可完全防止休克所致内毒素血症的发生,血浆内毒素峰值显著低于对照组〔74.0±22.5)对(13.8±6.8)pg/ml,P<0.05。〕烫伤8小时治疗组血浆内毒素均值降低42.4%。同时,rBPI21处理不同程度地抑制动物肺、肝、肠、肾等组织LBPmRNA表达水平(P<0.05~0.01)。病理形态学检查显示治疗组严重休克后脏器损害明显减轻,动物48小时存活率提高31.3百分点(68.8%对37.5%,P=0.08)。结论:严重创伤早期应用rBPI21能减轻内毒素血症诱发的多器官损害及改善动物预后,其作用机理与rBPI21对组织LBPmRNA表达的下调效应相关
Objective: To investigate the effect of lipopolysaccharide binding protein (LBP) on multiple organ damage induced by severe traumatic intestinal endotoxemia and the preventive and therapeutic effects of bactericidal / permeability increasing protein (BPI). Methods: The rats were subjected to severe hemorrhagic shock (30-35mmHg, 180min) and 35% Ⅲ ° scald. The levels of endotoxin, expression of LBP mRNA in lung, liver, intestine and kidney were observed by using recombinant BPI (rBPI21) Organ pathological changes and the impact of animal survival. Results: The administration of rBPI21 could completely prevent endotoxemia induced by shock. The peak value of plasma endotoxin was significantly lower than that of control group (74.0 ± 22.5 vs 13.8 ± 6.8 pg / ml, P <0.05. 〕 Burn for 8 hours in the treatment group plasma endotoxin mean decreased 42.4%. At the same time, rBPI21 inhibited the expression of LBP mRNA in lung, liver, intestine, kidney and other tissues to varying degrees (P <0.05 ~ 0.01). Pathological examination showed that organ damage was significantly reduced in the treatment group after severe shock, and the survival rate of animals increased by 31.3% at 48 hours (68.8% vs 37.5%, P = 0.08). Conclusion: The early application of rBPI21 in severe trauma can reduce endotoxemia-induced multiple organ damage and improve animal prognosis, and its mechanism of action is related to down-regulation of LBP mRNA expression by rBPI21