一氧化氮与地塞米松对内毒素肺损伤治疗作用的比较

The comparison of the effects of nitric oxide and dexamethasone on endotoxin-induced lung injury in rats

目的比较一氧化氮(NO)与地塞米松(Dex)对内毒素所致大鼠肺损伤的治疗作用及机制。方法将30只大鼠随机分成对照组、内毒素(LPS)组、Dex组、NO组、Dex+NO组,每组6只。通过LPS静脉注射制备大鼠肺损伤模型,观察不同干预方式(Dex腹腔注射和/或NO吸入)对肺损伤的治疗作用。结果LPS组大鼠肺组织出现水肿、出血,大量炎症细胞浸润及弥漫性肺泡塌陷,支气管肺泡灌洗液(BALF)中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)及IL-8水平显著升高,肺组织中核因子κB(NF-κB)核阳性表达细胞增多,糖皮质激素受体(GR)核阳性细胞表达下降,与对照组比较有显著差异(P均<0.05)。予以Dex腹腔注射或/和NO吸入干预后,大鼠肺组织肺泡水肿、炎症细胞浸润及出血均不同程度减轻;BALF中TNF-α、IL-1β及IL-8水平较LPS组降低(P均<0.05);肺组织中NF-κB核阳性表达细胞减少,与LPS组比较有显著差异(P<0.05);干预组肺组织GR核阳性细胞较LPS组明显增多(P<0.01),其中NO组肺组织GR阳性表达高于Dex组(P<0.05)。结论NO及Dex能有效减轻LPS所致的肺部炎症反应,NO还能提高肺损伤时肺组织内GR的表达,增强糖皮质激素的抗炎效果。

Objective To compare the effects of nitric oxide（NO） and dexamethasone（Dex） on endotoxin-induced lung injury in rats. methods Thirty rats were divided intκo 5 groups randomly, ie. a control group, a lipopolysaccharide（LPS） group, a Dex group, a NO group, and a Dex ＋ NO group. Lung injury model was established by LPS injection intravenously. Results Compared with the control group, there were alveolar edema, hemorrhage, neutrophilic alveolitis and diffuse alveolar damage in lung tissue, high levels of tumor necrosis factor-α （TNF-α）, interleukin-1β （IL-1β） and βL-8 in bronchalveolar lavage fluid （ BALF）, increased nuclear factor kappa B（NF-κB） nuclear-positive cells and lowered glucocorticoid receptor（GR） nuclear-positive cells in the lung tissue of the LPS group. Mter NO and/or Dex therapy, alveolar edema, hemorrhage, neutrophilic infiltration alleviated to different extent. The levels of TNF-α, IL-1β and IL-8 in BALF and the amount of NF-κB nuclear-positive cells decreased, and GR nuclear-positive cells increased significantly compared with the LPS group which was higher in the NO group than in the Dex group （ P 〈 0.05）. Conclusions NO and Dex can alleviate pulmonary inflammation and injury induced by LPS. NO can enhance the anti-inflammation effect of glucocorticoid through increasing the GR expression in lung.