N-乙酰半胱氨酸对感染性休克小鼠肺损伤保护作用的研究

Protective effect of N-acetylcysteine on lung injury in septic shock mice

目的探讨N-乙酰半胱氨酸(NAC)能否通过抗氧化应激、抗炎作用,起到减轻感染性休克小鼠肺损伤的作用。方法采用随机数字表法将30只小鼠分为对照组、模型组和NAC干预组3组,每组10只。模型组和NAC干预组腹腔注射脂多糖(LPS)(25 mg/kg,溶于0.2 ml 0.9%氯化钠注射液)制备内毒素诱发感染性休克模型,对照组则腹腔内注射等量0.9%氯化钠注射液。NAC干预组注射LPS后即刻腹腔注射NAC(300 mg/kg,溶于0.2 ml 0.9%氯化钠注射液),而对照组和模型组腹腔注射等量0.9%氯化钠注射液。6 h后处死小鼠,光镜下观察肺组织形态学变化,并进行肺组织病理损伤评分。采用ELISA法测定肺组织中炎症介质IL-6、TNF-α水平,采用比色法测定肺组织中氧化应激产物丙二醛(MDA)含量和抗氧化酶超氧化物歧化酶(SOD)活性。结果与对照组比较,模型组和NAC干预组小鼠肺组织病理损伤评分、IL-6、TNF-α水平、MDA含量均升高,SOD活性降低(均P<0.05);与模型组比较,NAC干预组小鼠肺组织病理损伤评分、IL-6、TNF-α水平、MDA含量均降低,SOD活性升高(均P<0.05)。结论NAC可减轻LPS诱导的感染性休克小鼠肺损伤的严重程度,使肺组织中抗氧化酶水平升高,而氧化应激产物和炎症介质水平降低。

Objective To investigate the effect of N-acetylcysteine(NAC)on lung injury in mice with septic shock.Methods Thirty healthy C57BL/6 mice were divided into 3 groups:the control group,the LPS group and the NAC group.The endotoxin-induced septic shock model was induced by intraperitoneal injection with 25 mg/kg lipopolysaccharide(LPS)in LPS group and NAC group,while the control group was intraperitoneally injected with equal volume of NS.NAC(300 mg/kg body weight)was injected into the abdominal cavity immediately after LPS injection in the NAC group,and the same dose of NS was injected in the control group and LPS group.The mice were sacrificed after 6 h.The pathological change in lung tissue was observed.The IL-6 and TNF-αlevels in lung tissue were detected,the activity of SOD and the concentration of MDA were determined.Results Compared with the control group,the lung injury was obvious and the levels of IL-6,TNF-α,MDA was increased,while the level of SOD was decreased significantly in LPS group(all P<0.05).Compared with the LPS group,the lung injury was alleviated and the levels of IL-6,TNF-α,MDA were reduced,while the level of SOD was increased significantly in NAC group(all P<0.05).Conclusion NAC can mitigate the severity of lung injury,increase the antioxidant index,and reduce the levels of oxidative stress injury index and inflammatory mediators in lung tissue of mice with LPS-induced septic shock.