脓毒症大鼠循环及组织内毒素的动态变化

The tissue distribution of endotoxin in septic rats

目的 :探讨脓毒症时组织内毒素的分布特征及其与多器官损害的关系。方法 :采用盲肠结扎穿孔 (CLP)致大鼠脓毒症模型 ,分别于伤前及伤后 2、 8、 16h测定血浆及组织内毒素含量。结果 :CLP后 2h血浆内毒素含量急剧增加 ,约为术前值的 17 1倍 ,其后迅速下降 ;伤后组织内毒素水平均不同程度上升 ,其中以肝组织升高幅度最大。肝组织内毒素水平于 8h达峰值 ,肺组织内毒素则持续升高 ,而肾组织其含量各时相点无显著性差异 (P >0 0 5 )。同时 ,反映肝、肺、肾等脏器功能指标均呈现不同程度的异常改变 ;相关分析表明 ,血浆内毒素与肺组织髓过氧化物酶活性显著正相关 (P <0 0 1)。结论 :CLP后循环内毒素水平急剧升高 ,并迅速分布至肝、肺、肾等组织 ,引起局部组织内毒素积聚 ;而组织内毒素可刺激机体炎症反应 ,参与脓毒症的发病过程。

Objective:To investigate the time course and tissue distribution of endotoxin in the development of multiple organ damage associated with polymicrobial sepsis.Methods:Wistar rats were subjected to polymicrobial sepsis induced by cecal ligation and puncture(CLP),both plasma and tissue endotoxin levels were measured before and 2,8 and 16 hours after the procedure.Results:It was found that plasma endotoxin concentration markedly increased at 2 hours after CLP(17 1 fold),and then declined at 8 hours,but was still higher than normal controls(P<0 05).Endotoxin levels in hepatic as well as pulmonary tissues significantly increased and maintained relatively high values throughout the observation period;however,no significant changes were found in renal endotoxin levels(P>0 05).Meanwhile,organ functional parameters including serum GPT,Cr levels and pulmonary myeloperoxidase(MPO)activities significantly increased in animals following CLP.There was a positive correlation between plasma endotoxin levels and pulmonary MPO activities(P<0 01).Conclusion:Severe intra abdominal infection after CLP could result in marked elevation of circulating endotoxin levels which,in turn,was rapidly distributed to the various organs such as liver,lungs,and kidneys.Endotoxin accumulated in tissues may be involved in the development of systemic inflammatory response and subsequent sepsis syndrome associated with polymicrobial infection.