N-乙酰半胱氨酸腹腔注射对LPS诱导小鼠急性肺损伤的预防作用观察  

Preventive effect of intraperitoneal injection of N-acetylcysteine on LPS-induced acute lung injury in mice

作　　者：冯艳 王荣丽 FENG Yan;WANG Rongli(The Affiliated Hospital of Southwest Medical University,Luzhou 646000,China)

机构地区：[1]西南医科大学附属医院

出　　处：《山东医药》2019年第33期44-47,共4页Shandong Medical Journal

摘　　要：目的探讨N-乙酰半胱氨酸(NAC)预先腹腔注射对脂多糖(LPS)诱导急性肺损伤(ALI)小鼠的预防作用及其机制探讨。方法30只BALB/c雌性小鼠,随机分为NAC 1、2、3组,模型组,对照组。NAC 1、2、3组分别腹腔注射100、200、300 mg/kg NAC,0.5 h后小鼠鼻孔滴10μg LPS,模型组鼻腔滴入10μg LPS,对照组鼻腔滴入50μL PBS。各组小鼠于滴鼻处理后7 h处死,取出双肺,光镜下观察肺组织学变化,测定肺湿干重比(W/D),ELISA法检测肺组织中髓过氧化物酶(MPO)、肿瘤坏死因子-α(TNF-α)、血管细胞黏附分子-1(VCAM-1),Western blotting法检测肺组织p-JNK蛋白。结果与模型组相比,NAC 1、2、3组肺泡间隔变窄及炎性细浸润减少,模型组肺泡间隔增宽及大量炎性细胞浸润。与对照组相比,模型组肺W/D及肺组织MPO活性,TNF-α、VCAM-1含量,p-JNK蛋白相对表达量升高(P均<0.05)。与模型组相比,NAC 1、2、3组肺W/D及肺组织MPO活性,TNF-α、VCAM-1含量,p-JNK蛋白相对表达量降低(P均<0.05),且呈剂量依赖性降低。结论NAC能够有效预防LPS诱导的ALI小鼠肺损伤,可能是通过抑制JNK信号通路激活发挥作用的。Objective To explore the preventive effect and the possible mechanism of pre-intraperitoneal injection of N-acetylcysteine(NAC)on lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice.Methods Thirty male BALB/c mice were randomly divided into the NAC 1 group,NAC 2 group,NAC 3 group,model group,and control group.The mice in the NAC 1,2 and 3 groups were given intraperitoneal injection of 100,200,and 300 mg/kg NAC at 0.5 h before injury.The mice in the model group were given LPS 10μg by intranasal instillation,and the mice in the control group were given PBS 50μL by intranasal instillation.All the mice were killed at 7 h after intranasal instillation and both lungs were removed.The pathologic structure of lung tissues were observed under light microscope and the wet weight/dry weight ratio of lung tissues were measured.The MPO activity,tumor necrosis factor-α(TNF-α)content and VCAM-1 content in the lung homogenate of mice were measured by ELISA.The expression of p-JNK protein in the lung tissues was detected by Western blotting.Results Compared with the model group,alveolus intervals became narrow and inflammatory cell infiltration decreased in the NAC intervention groups.Compared with the control group,pulmonary alveolus intervals became broad and a large number of inflammatory cells infiltrated in the model group.Compared with the control group,the lung tissue W/D,MPO activity,TNF-αcontent,VCAM-1 content,and relative expression of p-JNK protein increased in the model group(all P<0.05).Compared with the model group,the lung tissue W/D,MPO activity,TNF-αcontent,VCAM-1 content,and relative expression of p-JNK protein decreased in the NAC1,2 and 3 groups(all P<0.05).Meanwhile,the protective effects were in a dose-dependent manner.Conclusions NAC can effectively prevent LPS-induced ALI in mice by inhibiting the activation of JNK signaling pathway.

关 键 词：N-乙酰半胱氨酸 急性肺损伤 炎症信号通路 c-Jun-氨基末端激酶信号通路 髓过氧化物酶 肿瘤坏死因子-α 血管细胞黏附分子-1 

分 类 号：R657.5[医药卫生—外科学]