内毒素耐受大鼠与正常大鼠急性肺损伤反应比较

The pulmonary inflammation and acute lung injury in endotoxin tolerant rats

目的 动态观察内毒素耐受 (ET)大鼠在内毒素血症时肺部炎症反应和肺损伤与正常对照 (NC)大鼠的异同。方法 SD大鼠腹腔注射脂多糖 (LPS) 0 6mg·kg 1·d 1,连续 4d ,建立ET模型。第 5d腹腔注射 6mg/kgLPS。在注射大剂量LPS前、后不同时间点进行外周血和支气管肺泡灌洗液 (BALF)细胞学检查 ,以及肺组织病理学检查 ,测定BALF中白蛋白及其与血清白蛋白的比值衡量肺微血管通透性。结果 ET大鼠注射大剂量LPS后 ,未出现类似NC大鼠的体重减轻、肺部微血管通透性升高 (6h至高峰 )以及肺组织灶性中性粒细胞 (PMN)浸润和炎症反应。NC组 2 4h外周血PMN明显升高 ,而ET组始终以淋巴细胞为主 ;NC组BALF中PMN百分率 2h即升高 ,2 4h时为(8 0 0 0± 2 896) % ,而ET组始终小于 1%。结论 内毒素耐受可减轻内毒素血症引起以PMN浸润为特点的急性肺部炎症反应和肺损伤 ,提示内毒素耐受可能有助于防治急性呼吸窘迫综合征。

Objective To investigate the endotoxemia initiated systemic and pulmonary inflammation and acute lung injury in endotoxin tolerant rats MethodsEndotoxi n tolerance (ET) models of SD rats were induced by four daily intraperitoneal in jections of 0 6 mg·kg -1 ·d -1 Escherichia coli LPS (serotype 055:B5).Normal control (NC) rats received intraperitoneal injections of the sa me volume saline On the fifth day,rats were injected with high dose of LPS (6 mg/kg) to induce endotoxemia and lung inflammation Blood,left bronchoalveolar lavage fluid (BALF) and right lung tissue were collected before and 2,6,24,48 ,72 hours after the high dose injection of LPS (six rats for each time point) Cytological examination of blood and BALF and histopathological examination wer e performed Bromine methylphenol green was adopted for measurement of serum alb umin BALF albumin was measured by en z yme-linked immunosorbent assay (ELISA) and adjusted by the ratio to serum album in to evaluate the permeability of pulmonary microvascular Results The symptomes such as less activity,accelerated respiratory rate and weight loss in NC rats was not found in ET rats after the high dose injectio n of LPS BALF albumin as well as the ratio of BALF albumin to serum albumin in c reasedt 2 hours after injection of 6 mg/kg LPS and reached their zenith at 6 hou rs in NC rats,while no increase in ET rats In NC rats the blood white cell dif f erentiating shifted from lymphocyte to PMN,and PMN percentage of BALF also incr eased from (0 443±0 345)% to (8 000±2 896)% with its peak at 24 hours a fter the injection (P<0 001) in line with pulmonary path ological study which showed PMN accumulated in lung and exudates.None of those cytological and pathological variation were observed in ET rats ConclusionThe alleviation of endotoxemia initiated acute syst emic response and neutrophilic lung inflammation in ET rats suggested that ET co uld be used to prevent or treat ALI/ARDS