罗红霉素对哮喘大鼠NF-κB 及气道炎症的影响

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (7): 748-753.

罗红霉素对哮喘大鼠NF-κB 及气道炎症的影响

颜孙舜, 戴元荣, 吴立琴, 夏晓东

温州医学院附属第二医院呼吸内科, 温州325027, 浙江

收稿日期:2009-01-20 修回日期:2009-04-20 出版日期:2009-07-26 发布日期:2020-10-30
通讯作者: 戴元荣, 男, 主任医师, 硕士生导师, 研究方向:支气管哮喘的治疗。Tel:0577-88879063 　E-mail:daiyr@sina.com
作者简介:颜孙舜, 男, 硕士, 住院医师, 研究方向:支气管哮喘的治疗。Tel:13588922261 　E-mail:yan3s@163.com
基金资助:
浙江省科技厅资助基金(2006C33074);温州市科技局资助基金(Y20070136)

Effects of roxithromycin on NF-κB activity and bronchial hyperresponsiveness of asthma rats

YAN Sun-shun, DAI Yuan-rong, WU Li-qin, XIA Xiao-dong

Department of Respiration, Second Affiliated Hospital of Wenzhou Medical College, Wenzhou 325027, Zhejiang, China

Received:2009-01-20 Revised:2009-04-20 Online:2009-07-26 Published:2020-10-30

摘要/Abstract

摘要： 目的:观察罗红霉素对哮喘大鼠NF-κB、气道炎症、气道高反应性的影响。方法:30 只雄性SD 大鼠随机分成正常对照组(C 组)、哮喘组(A组)、罗红霉素组(R 组), 每组10 只。用卵白蛋白(OVA) 制备哮喘大鼠模型。各组大鼠在末次激发后24 h, 检测气道反应性后放血处死;ELISA 测定支气管肺泡灌洗液(BALF) 中的IL-4、IL-5、IFN-γ的浓度;免疫组化检测支气管上皮NF-κB p65 活化。结果:哮喘组大鼠气道反应性高于对照组(P<0.01), 罗红霉素组与哮喘组比较气道反应性下降(P<0.05);BALF 中IL-4、IL-5, 哮喘组含量均高于对照组(P<0.01), 罗红霉素组均低于哮喘组(P<0.01), 罗红霉素组BALF 中IFN-γ低于对照组(P<0.01) 但高于哮喘组;哮喘组大鼠支气管上皮NF-κB 蛋白的活化明显高于对照组, 罗红霉素组低于哮喘组(P<0.01)。支气管上皮NF-κB p65 活化与BALF 中的IL-4、IL-5 的含量呈显著正相关(r=0.856, P<0.01;r=0.912, P<0.01);大鼠BALF 中的IL-4、IL-5 的含量与Raw 增加25%时(PC25Raw) 呈显著负相关(r=-0.713,P<0.01;r=-0.772, P<0.01), 与Cdyn 下降15%时(PC15Cdyn) 呈显著负相关(r=-0.738, P<0.01;r=-0.818, P<0.01)。结论:罗红霉素可能部分通过抑制NF-κB 活性而纠正哮喘Th1Th2 细胞因子失衡, 罗红霉素降低哮喘大鼠的气道反应性可能和减少IL-4、IL-5 的表达有关。

关键词: 哮喘, 罗红霉素, NF-κB, 支气管高反应性

Abstract: AIM: To investigate the effect of roxithromycin on the NF-κB activity, the airway inflammation and bronchial hyperresponsiveness of asthma rats. METHODS: Thirty male adult Sprague-Dawley rats were randomly divided into the control group(Group C, n=10), asthma group (Group A, n=10) and roxith group(Group R, n=10).The asthma model was induced by ovalbumin and Al(OH) 3.The airway reactivity was detected and then rats in each group were sacrificed after 24 hours for the last provocation.The concentrations of IL-4, IL-5 and IFN-γin bronchoalveolar lavage fluid (BALF) were measured by ELISA, and the activity of NF-κB protein in bronchial epithelium was detected by immunohistochemistry.RESULTS: Compared with Group C, the airway reactivity in Group A was increased(P<0.01).Compared with Group A, the airway reactivity in Group R was decreased (P<0.05).Compared with Group A, the concentrations of IL-4, IL-5 in BALF in Group C were decreased (all P<0.01) and those in Group R were decreased (all P<0.01).The concentration of IFN-γ in BALF in Group R was significantly less than that in Group C (P<0.01) but was higher than that in Group A (P<0.01).The activity of NF-κB protein in bronchial epithelial in Group A was significantly higher than that in Group C (P<0.01) and that in Group R was less than that in Group A (P<0.01).There were significantly positive correlation between the activity of NF-κB p65 in bronchial epithelium and the concentrations of IL-4, IL-5 in BALF (r=0.856, P<0.01;r=0.912, P<0.01).There were significantly negative correlation between the concentrations of IL-4 and IL-5 in BALF and PC25Raw and PC15Cdyn (r=-0.713, P<0.01;r=-0.772, P<0.01, r=-0.738, P<0.01;r=-0.818, P<0.01, respectively).CONCLUSION: Roxithromycin can significantly inhibit the activity of NF-κB and retrieve the imbalance of Th1/Th2 cytokine in asthma.The airway reactivity of asthma rats is decreased by roxithromycin which may be related to the reduction of IL-4 and IL-5 expression

Key words: asthma, roxithromycin, NF-κB, bronchial hyperresponsiveness

中图分类号:

颜孙舜, 戴元荣, 吴立琴, 夏晓东. 罗红霉素对哮喘大鼠NF-κB 及气道炎症的影响[J]. 中国临床药理学与治疗学, 2009, 14(7): 748-753.

YAN Sun-shun, DAI Yuan-rong, WU Li-qin, XIA Xiao-dong. Effects of roxithromycin on NF-κB activity and bronchial hyperresponsiveness of asthma rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(7): 748-753.

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