一种创伤感染致多器官功能障碍综合征动物模型的建立

目的 复制符合临床特征且简便易行的创伤感染双相打击致多器官功能障碍综合征(MODS)动物模型,为进一步探讨其发病机制和治疗方法奠定基础.方法 6月龄Wistar雄性大鼠,体重(203.5±11.4)g.随机分为单纯创伤组(T组)和创伤感染序贯致MODS组(M组).钳夹大鼠肢体造成多发性闭合型骨折和广泛性软组织挫伤,M组12 h后致背部30%总体表面积(TBSA)Ⅲ度烫伤,并创面涂布绿脓杆菌.分别于创伤前以及创伤后24、48、96和120 h观察动物活动和创面情况,测定体重、体温、心率,并检测各时间点大鼠血浆及肝脏内毒素水平以及心、肝、肾、脑、小肠的功能变化,全身炎症反应发生率、MODS发生率及死亡率,同时对重要脏器进行组织病理学观察.结果 M组大鼠创伤48 h后,丙氨酸转氨酶(ALT)、总胆红素(Tbil)、血尿素氮(BUN)、血肌酐(Cr)、天冬氨酸转氨酶(AST)、肌酸磷酸激酶(CPK)的最高值均显著高于伤前自身对照值(P均＜0.05),且与T组比较差异有统计学意义(P均＜0.05);48 h后病理变化明显,大鼠处于若干脏器功能衰竭早期伴若干脏器功能受损期;内毒素水平在伤后96 h增至峰值,达到基础值的8.36倍;伤后96 h内毒素水平与脏器功能的变化具有明显的相关性(r=0.927 2),MODS发生率为86%,死亡率30%;伤后120 h,MODS发生率为100%,死亡率50%.结论 本模型较好地模拟了临床创伤继发感染后发展为MODS的过程,感染过程符合临床经过,内毒素释放稳定,机体反应充分,是用于创伤导致MODS发病机制和治疗方法研究较好的动物模型.

An experimental study of a rat model with MODS as a result of trauma induced infection

OBJECTIVE: To reproduce an animal model of multiple organ dysfunction syndrome (MODS) which was caused by two "hits" (injury and infection), to explore the potential aetiology and strategies of treatment. METHODS: The rats' extremities were crushed, resulting in severe injury with multiple closed fractures and extensive contusion of soft tissues. After 12 hours, a thirty percent total body surface area III (TBSA III) burns contaminated by Pseudomonas aeruginosa was inflicted upon the injury rats in MODS group. Rats'activities and wound appearance were observed, body weight, temperature, heart rate were recorded, and the blood lipopolysaccharide (LPS) level, the functional changes in all major organs, the occurrence rate of inflammatory reactions, the mortality of MODS and morbidity, and the pathological changes of the major organs were monitored at 24, 48, 96, 120 hours. RESULTS: To compare with pre-injury states and control group there were marked increases in alanine aminotransferase (ALT), total bilirubin (TBil), blood urea nitrogen (BUN), creatinine (Cr), aspartate aminotransferase (AST), creatine phosphokinase (CPK) contents 48 hours after the injuries (all P<0.05). When compared with the control group, there was significant difference (P<0.05). After 48 hours, there were obvious changes in pathology, the rats were in the early stage of MODS along with signs of damage to several organs. There was a typical relationship between LPS and organ functional changes. The LPS level peaked within 96 hours after the injury, the level was 8.36 folds of basic level. After 96 hours, there was correlation between LPS and the change of organ function (r=0.927 2). The incidence of MODS was 86%, and the mortality rate reached 30% in 96 hours after injury. At 120 hours after the injury, MODS was found in all the rats and the mortality rate reached 50%. CONCLUSION: This model seems to mimick the development of MODS which occurs after serious injuries followed by infection. The process of infection is coincidental with clinical picture, and LPS was released steadily with full body reaction. This animal model provides us an excellent opportunity to explore the pathogenesis and treatment of MODS after trauma.