不同因素致急性肺损伤大鼠TNF-α、IL-6的释放水平及地塞米松的影响

The release level of TNF-α and IL-6 and the effect of dexamethasone in the acute lung injury rats of which induced by different injuries

目的 探讨TNF α和IL 6在急性肺损伤中 (ALI)的作用和地塞米松的治疗意义 ;方法 本实验通过静脉注射内毒素(LPS)和盲肠结扎穿孔 (CLP)复制大鼠ALI模型 ,观察在这两种ALI模型早期 ,动脉血氧分压 (PaO2 )和肺湿干重比率 (W/D)、血浆促炎症细胞因子TNF α、IL 6的变化 ,以及地塞米松干预的影响。结果 ①在LPS刺激 1 2h和CLP 2 4h大鼠PaO2 均显著降低 ,W/D显著增加 ,在同一时相LPS组损伤较CLP组重 ;地塞米松能减轻两组ALI模型大鼠PaO2 的降低和W/D的增加。②两种模型大鼠血浆中TNF α的含量先迅速增加 ,后逐渐降低 ,IL 6的浓度逐渐增加 ;LPS组TNF α的峰值浓度出现较CLP组早 ,IL 6的浓度高于CLP组 ;地塞米松能显著降低两组模型中TNF α的峰值浓度和IL 6浓度的增加。结论 血浆TNF α峰值浓度出现的早晚和IL 6浓度的水平可能反映损伤的严重程度。糖皮质激素对LPS刺激和CLP大鼠ALI有保护作用 ,可能在ALI早期有治疗应用价值。

Objective To explore the effects of tumor necrosis factor α(TNF α)and interleukin 6 (IL 6) on acute lung injury (ALI) and the therapeutic value of dexamethasone. Methods Two acute lung injury models were replicated by intravenous injection of lipopolysaccharide (LPS) and by cecum ligation and puncture (CLP) in rats.The changes of arterial blood pressure (PaO 2), wet (W) and dry (D) ratio (W/D) of lung weight, plasma levels of TNF α and IL 6 and the effects of dexamethasone on the changes were observed. Results In the groups of treated with LPS for 12 h and CLP for 24 h, PaO 2 was significantly decreased and W/D ratio was markedly increased. The lung injury were more serious in LPS treated groups than CLP groups in the same stage. Dexamethasone could abate the decrease of PaO 2 and increase of W/D ratio. In the two models,TNF α levels in plasma were increased at first and then decreased,but IL 6 levels were increased gradually. In LPS treated groups,the peak levels of TNF α were appeared earlier and IL 6 levels were higher than in CLP groups. Dexamethasone could decrease the TNF α peak levels and IL 6 levels significantly. Conclusion The time of peak level of TNF α and IL 6 level may reflex the severity of the acute lung injury. Glucocorticoids have an effect for protecting acute lung injury and may be used to treat ALI in early stage.