N-乙酰半胱氨酸对哮喘小鼠模型气道炎症和氧化应激的影响

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摘要［摘要］目的: 探讨N-乙酰半胱氨酸(N-acetylcysteine，NAC)对哮喘模型小鼠气道炎症和氧化应激反应的影响及可能的机制。方法: 选择18只SPF级BALB/c雌性小鼠，随机均分为对照组、哮喘组、N-乙酰半胱氨酸组，每组6只。哮喘组、N-乙酰半胱氨酸组雾化激发构建小鼠哮喘模型，N-乙酰半胱氨酸组每次雾化开始前30 min灌胃给药N-乙酰半胱氨酸(300 mg/kg)，对照组予等量PBS处理，末次激发后24 h内取检测标本。收集支气管肺泡灌洗液行炎症细胞计数；ELISA法检测血清中细胞因子IL-5、IL-13和IFN-γ含量；取小鼠肺组织行HE染色观察病理变化并行炎症评分；比色法测定肺组织中丙二醛和谷胱甘肽含量；实时荧光定量PCR测肺组织核因子E2相关因子2(nuclear factor erythroid 2 related factor 2，Nrf2)、血红素加氧酶-1( heme oxygenase-1，HO-1)mRNA表达水平。结果：与对照组相比，哮喘组肺组织大量炎性细胞浸润、肺泡结构破坏明显，炎症细胞数、IL-5、IL-13含量、炎症评分、丙二醛含量均明显升高(P均<0.05)，IFN-γ和谷胱甘肽含量均明显降低(P均<0.05)，Nrf2和HO-1 mRNA表达差异无统计学意义(P＞0.05)；与哮喘组相比，N-乙酰半胱氨酸组肺组织炎症细胞浸润减少、肺泡结构破坏减轻，炎症细胞数、IL-5和IL-13含量、炎症评分、丙二醛含量均明显降低(P均<0.05)，IFN-γ、谷胱甘肽含量和Nrf2、HO-1 mRNA表达均明显升高(P均<0.05)。结论： NAC可减轻哮喘小鼠气道炎症及氧化应激反应，可能通过激活Nrf2/HO-1信号通路发挥保护作用。

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	徐莉莉1
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	尚璐璐1
	丁慢玲1
	郑金旭1

关键词 ：哮喘, N-乙酰半胱氨酸, 气道炎症, 氧化应激, 组织核因子E2相关因子2, 血红素加氧酶-1

Abstract：Objective: To investigate the effect of N-acetylcysteine (NAC) on airway inflammation, oxidative stress in asthma model mice and its potential mechanism. Methods: Eighteen female BALB/c mice were randomly divided into control group, asthma group, and N-acetylcysteine(NAC) group, with 6 in each group. Asthma group and NAC group were atomized to construct asthma model, and NAC group was given NAC (300 mg/kg) by intragastric instillation 30 min before atomization, and control group was treated with the same volume of PBS. Samples were harvested within 24 h after the end of nebulization. Collection of bronchoalveolar lavage fluid was used to count inflammatory cells. The levels of serum cytokines IL-13, IL-5 and IFN-γ were measured by ELISA. HE staining was used to observe the pathological changes of mice lung tissue, and inflammation score was performed. The levels of malondialdehyde and glutathione(GSH) in lung tissue were measured by colorimetry. The expression of nuclear factor erythroid 2 related factor 2(Nrf2) and heme oxygenase1(HO-1) in lung tissue were measured by quantitative real-time PCR method. Results: Compared with the control group, there were lots of inflammatory cells infiltration in the lung tissue, the alveolar structure was obviously destroyed, the number of inflammatory cells, the levels of IL-5, IL-13, inflammation score, and the levels of malondialdehyde were significantly increased (all P<0.05), the levels of IFN-γ and GSH were significantly decreased(all P<0.05), the expression of Nrf2 mRNA and HO-1 mRNA showed no significant difference in asthma group. Compared with the asthma group, the infiltration of inflammatory cells in lung tissue and the destruction of alveolar structure were reduced, the number of inflammatory cells, IL-5, IL-13 contents, inflammation score, malondialdehyde contents were significantly decreased(all P<0.05), the contents of IFN-γ, GSH and the expression of Nrf2 mRNA and HO-1 mRNA were significantly increased in NAC group (all P<0.05). Conclusion: NAC could reduce airway inflammation and oxidative stress in asthmatic mice, which may be attributed to activation of Nrf2/HO-1 signaling pathway.

收稿日期: 2020-04-30

基金资助:江苏大学横向课题(8413210004);张家港市科技支撑计划(社会发展)项目(ZKS1724)

通讯作者: 郑金旭(通讯作者)，教授，博士生导师，E-mail：Jxuzh135@163.com

作者简介: 徐莉莉(1992—)，女，硕士研究生

引用本文:

徐莉莉1，张军2，尚璐璐1，丁慢玲1，郑金旭1. N-乙酰半胱氨酸对哮喘小鼠模型气道炎症和氧化应激的影响[J]. 江苏大学学报:医学版, 2021, 31(01): 56-60. XU Lili1， ZHANG Jun2， SHANG Lulu1， DING Manling1， ZHENG Jinxu1.

Effects of N-acetylcysteine on airway inflammation and oxidative stress in asthma model mice

. Journal of Jiangsu University(Medicine Edition), 2021, 31(01): 56-60.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2021/V31/I01/56

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