吸入一氧化氮对急性肺损伤大鼠肺组织炎症的影响

Nitric Oxide Inhalation Alleviates Lung Inflammation of Rats with Acute Lung Injury

目的观察吸入不同浓度一氧化氮(NO)对急性肺损伤(ALI)大鼠肺组织的影响。方法将24只SD大鼠随机分为对照组、ALI模型组、低浓度NO组和高浓度NO组,每组6只。ALI模型组、低浓度NO组和高浓度NO组气管内滴注脂多糖(LPS)复制大鼠急性肺损伤模型,对照组气管内滴注生理盐水。接动物呼吸机,对照组与ALI模型组吸入正常空气,低浓度NO组和高浓度NO组吸入的空气中加入20×10-6mg/L和100×10-6mg/L的NO。观察各组大鼠6h后的肺部病理学变化,进行肺部炎症评分。采用免疫组化检测大鼠气道Toll样受体4(TLR4)的表达,ELISA法检测肺组织匀浆IL-6的水平。结果TLR4及IL-6在对照组大鼠气道内有广泛分布和表达。ALI模型组大鼠支气管、肺内炎症程度明显高于对照组,主支气管和肺内细支气管上皮细胞内TLR4表达明显增强,IL-6的含量较正常组明显增加。低浓度NO组气管和主支气管的炎症程度明显减轻,TLR4及IL-6的表达量较ALI模型组组明显减少。但高浓度NO组肺组织炎症程度、TLR4表达与ALI模型组无显著差异,IL-6水平反而显著增高。结论吸入适当浓度NO可降低ALI时肺组织TLR4及IL-6表达的增高,减轻肺组织炎症。

Objective To observe the effects of nitric oxide（NO）inhalation on lung inflammation of acute lung injury（ALI）in rats.Methods Twenty-four SD rats were randomly divided into four groups,ie.a normal control group,an ALI group,a 20 ppm NO inhalation group,and a 100 ppm NO inhalation group.ALI model was established by LPS instillation intratracheally and the control group was instilled with normal saline.Then they were ventilated with normal air or NO at different levels,and sacrificed 6 hours later.Pathological changes were evaluated by HE staining.The expression of TLR4 in lung tissues was detected by immunohistochemistry.IL-6 level in lung homogenate was measured by ELISA.Results In the ALI group,the inflammation in bronchus and bronchioles was more apparently,and the expressions of TLR4 and IL-6 were elevated significantly compared with the control group.20 ppm NO inhalation significantly decreased the expression of TLR4 and IL-6,and alleviated the inflammation of ALI.However,100 ppm NO inhalation did not change TLR4 expression and lung inflammation significantly,and increased IL-6 level.Conclusions Inhalation low level of NO（20 ppm）can alleviate lung inflammation possibly by reducing the expression of TLR4 and IL-6.