N-乙酰半胱氨酸对 H9 N2猪流感病毒所致急性肺损伤小鼠的保护作用

摘要

AIM:To investigate the effects of N-acetylcysteine (NAC) on acute lung injury induced by H9N2 swine influenza virus ( SIV) in mice.METHODS: BALB/c mice were used to establish the animal model of acute lung injury by nasal inoculation of H9N2 SIV.The mice were divided into control group (without SIV infection), H9N2 SIV group (inoculation of H9N2 SIV) and NAC group (inoculation of H9N2 SIV plus pretreatment with NAC).The pulmonary edema was evaluated by determining the lung wet weight /dry weight ( W/D) ratio.The pathological changes of the lung tis-sues were observed .The concontrations of TNF-α, IL-1βand IL-6 in bronchoalveolar lavage fluid ( BALF) were meas-ured.The virus titer, T-SOD activity, MPO activity and MDA content in the homogenate of the lung tissues were detected . RESULTS:Treatment with NAC decreased the morality of infected mice , and significantly prolonged the survival time of infected mice .The pathological changes of the lung tissues , the lung W/D ratio and the lung index were relieved when SIV infected the mice treated with NAC .Treatment with NAC significantly decreased the infiltration of inflammatory cells inclu-ding macrophages, lymphocytes and neutrophils in the BALF .The levels of TNF-α, IL-6, IL-1βand MDA and the activity of MPO were also decreased.Treatment with NAC also significantly increased the T-SOD activity.CONCLUSION: The protective effect of NAC on the acute lung injury mouse model is related to suppression of the oxidative stress and inflamma -tory responses .%目的：探讨N-乙酰半胱氨酸（ NAC）对H9N2猪流感病毒所致急性肺损伤小鼠的保护作用。方法：采用BALB/c小鼠建立H9N2猪流感病毒诱导的急性肺损伤模型。实验小鼠在接种病毒前1 h腹腔注射NAC（10 mg/kg，稀释于生理盐水），此后连续使用5 d。检测肺湿重与干重比变化，评估肺水肿情况，观察肺组织的病理学变化，检测支气管肺泡灌洗液内炎症细胞、肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）及白细胞介素1β（IL-1β）的变化，同时检测肺组织匀浆中病毒的增殖、总超氧化物歧化酶（ T-SOD）和髓过氧化物酶（ MPO）活性以及丙二醛（ MDA）含量。结果：NAC能降低小鼠死亡率，延长小鼠存活时间，显著降低肺组织的病理学变化和肺水肿程度，并能降低巨噬细胞、淋巴细胞和中性粒细胞等炎症细胞的数量，同时降低TNF-α、IL-6、IL-1β和MDA的含量，抑制MPO的活性以及升高T-SOD的活性。结论：NAC减轻H9N2猪流感病毒诱导的小鼠急性肺损伤，其保护作用可能与减轻氧化应激作用和炎症反应相关。