核转录因子-κB及一氧化氮在急性肺损伤发生中的作用

The roles of nuclear factor-κB,inducible nitric oxide synthase,and nitric oxide in the mechanism of acute lung injury in rats

目的 探讨核转录因子 κB(NF κB)及诱导型一氧化氮合酶 (iNOS)、一氧化氮 (NO)在大鼠急性肺损伤 (ALI)发生机制中的作用 ,为临床治疗ALI寻找新的治疗措施提供理论依据。方法 应用脂多糖 (LPS)静脉注射复制大鼠ALI模型。将 32只SD大鼠随机分成 4组 :正常对照组 (NS组 )、ALI模型组 (LPS组 )、N 乙酰半胱氨酸 (NAC)干预组及地塞米松 (DXM)干预组 ,后两组分别以NAC(2 0 0mg/kg)和DXM(70mg/kg)预处理。各组大鼠均于注射LPS或生理盐水后 4h处死 ,观察肺病理改变 ,测定肺系数 ,免疫组化方法检测肺NF κB、iNOS染色强度 ,测定血清NO、丙二醛 (MDA)含量。结果 LPS组大鼠肺病理见明显ALI表现 ,肺NF κB、iNOS染色强度和血清NO亦明显高于NS组 (P <0 0 5 ) ,肺系数及血清MDA水平均明显高于NS组 (P <0 0 5 )。NAC干预组及DXM干预组肺NF κB、iNOS染色强度和血清NO均明显低于LPS组 (P <0 0 5 ) ,肺病理表现较LPS组明显好转 ,肺系数及MDA水平均明显低于LPS组 (P <0 0 5 )。结论 大鼠肺部NF κB活化 ,肺iNOS表达增多 ,大量NO生成共同参与了ALI的发生。抑制NF κB的表达 。

Objective To explore the roles of nuclear factor-κB (NF-κB),inducible nitric oxide synthase (iNOS),and nitric oxide (NO) in the mechanism of acute lung injury (ALI).Methods Lipopolysaccharide (LPS,5 mg/kg) was used to copy ALI rat models.Thirty-two adult SD rats were randomly divided into four groups:control group (NS group),ALI model group (LPS group), N-acetyl cysteine (NAC) pretreatment group (NAC group) and Dexamethasone (DXM) pretreatment group (DXM group).In the later two groups,NAC (200 mg/kg) or DXM (70 mg/kg) was injected intraperitoneally respectively 1 hour before LPS was given intravenously.Four hours after LPS injection,the animals were killed.Then the pathological manifestation of lungs was observed,the lung index was calculated,while the intension of NF-κB expression and iNOS expression in the lung,the concentration of NO and malondialdehyde (MDA) in serum was detected.Results Obvious ALI pathological manifestation in the lungs of LPS group rats was observed.Compared with NS group,the expression of NF-κB and iNOS in lungs and concentration of NO in serum increased significantly in LPS group (P<0.05)as well as lung index and concentration of MDA in serum (P<0.05).Compared with LPS group,the pathological manifestation in the lung was ameliorated and the expression of NF-κB and iNOS,the concentration of NO and MDA,and lung index decreased significantly in NAC group and DXM group (P<0.05).Conclusion NF-κB and iNOS-NO pathway were involved the pathogenesis of ALI in rat model and could be novel target molecules in prevention and treatment of ALI/ARDS.