内毒素预处理对大鼠急性肺损伤的影响

目的　探讨肺泡巨噬细胞核因子κB( NFκB)活性变化在内毒素所致大鼠急性肺损伤中的作用。方法　 Wistar大鼠 36只 ,12只腹腔连续 3d注射脂多糖 ( L PS) 0 .5、0 .5和 1.0 mg/ kg,第 4 d腹腔注射脂多糖 ( L PS) 6 mg/ kg( L PS预处理组 ) ;12只腹腔注射内毒素 6 m g/ kg(肺损伤组 ) ;12只为正常对照组 ,腹腔注射生理盐水。注射完毕后 4 h处死大鼠 ,取肺测定肺组织湿 /干质量比 ( W/ D) ;以 99Tc标记的血清白蛋白测定肺通透指数 ;从肺灌洗液中提取肺泡巨噬细胞核蛋白 ,用凝胶电泳迁移率 ( EMSA)方法检测 NFκB活性。各组肺进行病理组织学观察。结果　 L PS预处理组肺 W/ D及通透性显著低于肺损伤组 ,而 Pa O2 和碱剩余高于肺损伤组 ;且肺损伤组及 L PS预处理组的 NFκB活性皆显著升高 ( P均 <0 .0 5 ) ,L PS预处理组高于肺损伤组。结论　内毒素预处理可减轻内毒素造成的肺损伤 ,此现象可能与肺泡巨噬细胞 NFκB活性变化有关

Influence of lipopolysaccharide pretreatment on acute lung in jury indued by lipopolysaccharide in rats

OBJECTIVE: To evaluate the effect of lipopolysaccharide pretreatment on blocking the development of lipopolysaccharide (E.Coli O(55):B(5)) induced acute lung injury. The activity of nuclear factor-kappaB (NF-kappaB) in alveolar macrophages was assessed to elucidate its mechanism. METHODS: Thirty-six Wistar rats were divided into three groups: normal saline (A), lipopolysaccharide (B), lipopolysaccharide preconditioning (C). Rat model of acute lung injury was reproduced by administering intraperitoneally lipopolysaccharide in a dose of 6 mg/kg. Group A and B served as control. In the test group (group C) lipopolysaccharide was given intraperitoneally 0.5 mg/kg, 0.5 mg/kg and 1.0 mg/kg consecutively for 3 days before lipopolysaccharide challenge. Four hours after lipopolysaccharide/normal saline administration, the animals were killed. Blood gas was measured. And total protein of bronchoalveolar lavage fluid (BALF) was calculated by measuring the radioactivity of (99)Tc labeled serum albumin. Wet/dry ratios of the lungs of each group were determined. The nuclear protein of the alveolar macrophages was extracted from BALF, and the activity of NF-kappaB was assayed with electrophoretic mobility shift assay (EMSA). Microscopic examination of the lung was done. RESULTS: In group C, partial pressure of oxygen in artery (PaO(2)) was significantly higher than that in group B, and total protein content of BALF was significantly lower in group A and C than that in group B. Activity of NF-kappaB in group C was higher than group A and B. CONCLUSION: Lipopolysaccharide pretreatment can reduce the severity of acute lung injury induced by lipopolysaccharide challenge. This phenomenon may be related with change in the activity of NF-kappaB of the alveolar macrophages.