吉林大学学报(医学版) ›› 2018, Vol. 44 ›› Issue (05): 897-902.doi: 10.13481/j.1671-587x.20180502

• 基础研究 • 上一篇    下一篇

白藜芦醇对中性粒细胞性哮喘小鼠肺组织炎症的抑制作用及其机制

冉琴1, 张雷1, 张沄2, 邱玉环1, 袁谢芳2, 王孝芸2, 唐红梅2, 王星2, 李国平2   

  1. 1. 西南医科大学附属医院呼吸内科, 四川 泸州 646000;
    2. 西南医科大学附属医院炎症与变态反应实验室, 四川 泸州 646000
  • 收稿日期:2018-01-07 出版日期:2018-09-28 发布日期:2018-11-20
  • 通讯作者: 王星,实习研究员(Tel:0830-3165324,E-mail:wx_eliot_881014@163.com);李国平,教授,博士研究生导师(Tel:0830-3165324,E-mail:lzlgp@163.com) E-mail:wx_eliot_881014@163.com;lzlgp@163.com
  • 作者简介:冉琴(1992-),女,四川省广安市人,在读医学硕士,主要从事哮喘基础与临床方面的研究。
  • 基金资助:
    国家自然科学基金资助课题(81600024)

Inhibitory effect of resveratrol on pulmonary inflammation in mice with neutrophilic asthma and its mechanism

RAN Qin1, ZHANG Lei1, ZHANG Yun2, QIU Yuhuan1, YUAN Xiefang2, WANG Xiaoyun2, TANG Hongmei2, WANG Xing2, LI Guoping2   

  1. 1. Department of Respiratory Medicine, Affiliated Hospital, Southwest Medical University, Luzhou 646000, China;
    2. Inflammation and Allergy Laboratory, Affiliated Hospital, Southwest Medical University, Luzhou 646000, China
  • Received:2018-01-07 Online:2018-09-28 Published:2018-11-20

摘要: 目的:探讨白芦藜醇对中性粒细胞性哮喘小鼠肺组织炎症的抑制作用,并阐明其作用机制。方法:选取18只C57BL/6J雌性小鼠,采用脂多糖(LPS)+卵白蛋白(OVA)联合致敏方法建立中性粒细胞性哮喘小鼠模型,随机分为模型组(LPS+OVA组)、白藜芦醇组(Res组,于激发前2 h灌胃30 mg·kg-1白藜芦醇)和N-乙酰半胱氨酸组(NAC组,于激发前2 h灌胃3 mmol·kg-1 N-乙酰半胱氨酸);同时选取6只同周龄小鼠作为正常对照组(PBS组)。于乙酰甲胆碱雾化期间观察各组小鼠的行为学变化,采用肺功能仪分析小鼠气道高反应(AHR),光学显微镜观察支气管肺泡灌洗液(BALF)中细胞总数和炎症细胞,HE染色观察各组小鼠肺组织病理形态表现,酶联免疫法(ELISA)检测各组小鼠BALF上清中白细胞介素17(IL-17)水平,特异性荧光探针DCF-DA染色分析肺组织活性氧(ROS)水平,丙二醛(MDA)试剂盒检测肺组织匀浆中MDA水平。结果:与PBS组比较,LPS+OVA组小鼠Penh值、细胞总数、炎症细胞、气道炎症及评分均明显升高(P<0.05或P<0.01),BALF上清中IL-17水平明显升高(P<0.01),肺组织内ROS荧光强度明显升高,肺匀浆中MDA水平明显升高(P<0.01)。与LPS+OVA组比较,Res组和NAC组小鼠Penh值、细胞总数、炎症细胞、气道炎症及评分明显降低(P<0.05或P<0.01),BALF上清中IL-17水平均明显降低(P<0.05),肺组织内ROS荧光强度降低,肺匀浆中MDA水平明显降低(P<0.01)。结论:白藜芦醇能够有效抑制中性粒细胞性哮喘小鼠肺组织中的炎症反应,其机制可能与白藜芦醇抑制体内发生的氧化应激反应有关。

关键词: 中性粒细胞性哮喘, 白藜芦醇, 炎症, 氧化应激

Abstract: Objective:To investigate the inhibitory effect of resveratrol on the pulmonary inflammation in the mice with neutrophilic asthma, and to elucidate its mechanism. Methods:A total of 18 female C57BL/6J mice were selected.The mouse models of neutrophilic asthma were established by sensitization with lipopolysaccharide (LPS) and ovalbumin (OVA). The model mice were randomly divided into model group (LPS + OVA group), resveratrol group(Res group, intragastric administration of 30 mg·kg-1 resveratrol at 2 h before challenge) and N-acetylcysteine group (NAC group, intragastric administration of 3 mmol·kg-1 N-acetylcysteine at 2 h before challenge). Other 6 age-matched female C57BL/6J mice were choosen as normal control group (PBS group). The behavioral changes of mice in various groups were observed during the atomization with methacholine; the airway hyperresponsiveness (AHR) of mice was analyzed with a lung function instrument, and the total number of cells and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were observed with light microscope; the pathological changes of lung tissue were observe by HE staining; the levels of interleukin-17(IL-17) in the supernatant of BALF of the mice in various groups were detected by enzyme-linked immunosorbent assay (ELISA); the level of reactive oxygen species (ROS) in lung tissue was analyzed by specific fluorescent probe DCF-DA staining; the level of malondialdehyde (MDA) in lung homogenate was measured by MDA kit. Results:Compared with PBS group, the Penh value, total number of cells, inflammatory cells, airway inflammation and scores of the mice in LPS+OVA group were significantly increased (P<0.05 or P<0.01); the IL-17 level in BALF supernatant was significantly increased (P<0.01); the ROS fluorescence intensity in lung tissue was significantly increased, and the MDA level in lung homogenates was significantly increased (P<0.01). Compared with LPS + OVA group, the Penh value, total number of cells, inflammatory cells, airway inflammation and scores in Res group and NAC group were significantly decreased (P<0.05 or P<0.01); the IL-17 levels in BALF supernatant were significantly decreased (P<0.05 or P<0.01); the ROS fluorescence intensities in lung tissue were decreased, and the MDA levels in lung homogenates were significantly decreased (P<0.01). Conclusion:Resveratrol can effectively inhibit the inflammatory response of lung tissue in the mice with neutrophilic asthma, and its mechanism may be related to inhibiting the oxidative stress reaction.

Key words: neutrophilic asthma, resveratrol, inflammation, oxidative stress

中图分类号: 

  • R562