IL-8和IL-10在家兔内毒素性急性肺损伤中的作用

Effects of IL-8 and IL-10 in mediating lipopolysaccharide-induced acute lung injury in rabbits

目的探讨内毒素性急性肺损伤的机制。方法用间隔24h注射内毒素(LPS)制作家兔内毒素性肺损伤模型。成年雄性家兔静脉注射LPS3μgkg,24h后在机械通气下用微泵缓慢输注50μgkgLPS,待动态肺顺应性(Cdyn)下降到75%时分为两组:治疗组(n=8)静脉注射地塞米松(DEX)1mgkg;对照组(n=8)静脉注射与治疗组同等容积的生理盐水。动态观察不同时点血浆IL8和IL10水平的变化。将兔在地塞米松治疗后6h处死作形态学检查,并测定支气管肺泡灌洗液(BALF)PMN计数、肺组织和BALF中IL8和IL10的水平。结果两组血浆IL8和IL10水平均在Cdyn75%时,与基础状态相比,显著性升高(P<0.05)。血浆、肺组织、BALF中IL8水平在DEX治疗后均显著性降低(P<0.05)。肺组织、BALF中IL8与IL10的比值在DEX治疗后与对照组相比均显著性降低(P<0.05)。形态学结果表明DEX可明显减轻肺组织的损伤。结论IL8与IL10可能参与内毒素性肺损伤的发生发展。在Cdyn下降至75%时给予1mgkgDEX可能通过抑制IL8的产生而减轻肺损伤。

Objective To study the mechanism of acute lung injury （ALl） induced by lipopolysaccharide （LPS） in rabbits. Methods The model was produced by intravenous injection of 3μg/kg LPS and at 24 hours followed by infusion of 50μg/kg LPS for 2 hours. When pulmonary dynamic compliance （Cdyn） decreased to 75% of the baseline level, rabbits were randomly divided into two groups： treatment group and controls. Each group had 8 animals, treatment group was reeeired dexamethasone lmg/kg intravenously, while control group was receired 0.2 ml/kg 0.9% sodium chloride. Plasma interleukin-8 （IL-8） and interleukin-lO （IL-IO） levels were measured. 6 hours after administration of dexamethasone, the animals were killed. Lung tissue and bronchoalveolar lavage fluid （BALF） were collected for measurement of IL-8 and IL- 10, and amount of PMN in BALF. In addition, lung tissue was also used for histological examination. Results The levels of IL-8 and IL-10 were significantly higher at the time of 75 % Cdyn than those at the baseline in both groups （ P 〈 0.05）. The levels of IL-8 in plasma, lung tissue, BALF in treatment group significantly decreased （P 〈 0.05）. The ratios of IL- 8 to IL-10 in lung tissue and BALF in treatment group were significantly lower than those in control group （P 〈 0.05）. In addition, the injury and inflammatory cellular infiltration in the pulmonary stroma and alveoli in C group were much severe than those in T group. Conclusion IL-8 and IL-IO may play a role in the development of LPS-induced ALl. 1 mg/kg dexarnethasone early administered could reduce LPS-induced ALl in rabbits, which might be related to IL-8 decrease.