二次打击肺损伤大鼠肺组织中LBP的表达及山莨菪碱的保护作用

Expression of lipopolysaccharide binding protein mRNA in pulmonary tissues of rat with ‘two-hit’ acute lung injury and the protective effects of anisodamine in this event

目的 探讨机体遭受一次打击后 ,脂多糖结合蛋白 (LBP)对二次打击的增敏效应及山莨菪碱的保护机制。方法 用油酸 (OA ,0 .2ml/kg)和脂多糖 (LPS ,2mg/kg)两次致伤 ,复制大鼠急性肺损伤模型。用RT PCR检测肺组织中LBP、TNFα、IL 10mRNA的表达 ,并行病理组织学观察和动脉血气分析。结果 一次打击可使肺组织中LBP的表达明显增强 ,在此基础上行二次打击后 ,肺组织中TNFα和IL 10的表达增高 ;山莨菪碱干预可抑制LBP的上调 ,减少TNFα和IL 10的表达 ,病理改变也有所减轻。结论 第一次打击后LBP的反应性上调是使机体对第二次打击敏感性增加的重要机制 ,山莨菪碱可能通过抑制LBP的过度表达 ,阻断LBP对LPS的增敏作用 ,从而发挥其对肺损伤的防治作用。

Objective To investigate the potential role of lipopolysaccharide binding protein (LBP) in rat acute lung injury following ‘two hit' and the protective effects of anisodamine. Methods The animal model of acute lung injury was established with the oleic acid (OA, 0.2 ml/kg) and lipopolysaccharide (LPS, 2 mg/kg) in Wistar rats. LBP, TNFα and IL 10 mRNA expressions in pulmonary tissues were determined with RT PCR. The pathological changes of pulmonary tissues and arterial blood gas were observed. Results LBP mRNA expression was up regulated after injection of OA alone. The expressions of TNFα and IL 10 mRNA in rat treated with OA and LPS were higher than those in OA treated rats. Anisodamine inhibited the expressions of LBP, TNFα and IL 10 mRNA, and alleviated the pulmonary tissue damage. Conclusion The up regulation of LBP after the first hit with OA is an important mechanism of increasing sensitivity to second hit with LPS, and anisodamine has a protective effect on acute lung injury through down regulation of the LBP expression in pulmonary tissues.