标题：JunB在实验性支气管哮喘中的作用

      作者：李海燕 1*，郭 琦 2*，陈如冲 3，周一平 2，李 明 2，喻海琼 2，江 梅 3
    (1.广东医学院附属福田医院社康部，广东 深圳 518033；
2.广东医学院附属福田医院呼吸科，广东 深圳 518033；
3.广州呼吸疾病研究所(呼吸疾病国家重点实验室)，广东 广州 510120)

      卷次： 2013年24卷6期

      【摘要】 目的 探索激活蛋白-1 (Activator protein-1，AP-1)家族成员中参与构成哮喘病理生理特征的关键亚单
位，为哮喘治疗提供更精确和新颖分子靶点。方法 建立大鼠哮喘模型。130只雄性Wistar大鼠随机分为正常对照组、
哮喘空白组、c-Jun反义寡核苷酸(Antisense oligodeoxynucleotides，AS-ODNs)组、JunB AS-ODNs组、JunD AS-ODNs
组、c-Fos AS-ODNs组、FosB AS-ODNs组、Fra-1 AS-ODNs组、Fra-2 AS-ODNs组和无义寡核苷酸(Nonsense ODNs，
NS-ODNs)组。实施基因沉默后，HE染色计数支气管肺泡灌洗液中嗜酸粒细胞(Eosinophils，EOS)百分比，逆转录-聚合
酶链反应检测白介素(Interleukin，IL)-5 mRNA表达。结果 JunB AS-ODNs组的EOS百分比[(13.39±3.72)%]显著低
于哮喘空白组[(34.33±9.62)%]，差异有统计学意义(P<0.001)，但仍高于正常对照组[(5.61±1.76)%]，差异有统计学意义
(P<0.05)。其余ODNs组的EOS百分比与哮喘空白组的差异均无统计学意义(P>0.05)。与哮喘空白组比较，JunB
AS-ODNs组的 IL-5 mRNA表达被显著抑制[(0.554 2±0.082 9) vs (0.822 4±0.066 0)，P<0.001]，但亦仍高于正常对
照组[(0.323 7±0.057 7)，P<0.001]。其余ODNs组 IL-5 mRNAs表达与哮喘空白组比较，差异均无统计学意义
(P>0.05)。结论 在转录因子AP-1家族中，JunB亚单位可能决定哮喘大鼠气道慢性炎症，可能是新颖治疗
靶点。

      【关键词】 激活蛋白-1；亚单位；反义寡核苷酸；支气管哮喘

      【中图分类号】 R562.2+2 【文献标识码】 A 【文章编号】 1003—6350（2013）06—0781—04


Role of JunB in experimental bronchial asthma.
LI Hai-yan 1*, GUO Qi 2*, CHEN Ru-chong 3, ZHOU Yi-ping 2, LI
Ming 2, YU Hai-qiong 2, JIANG Mei 3. 1. Department of Primary Care, Futian Hospital Affiliated to Guangdong Medical
College, Shenzhen 518033, Guangdong, CHINA; 2. Department of Respiratory Medicine, Futian Hospital Affiliated to
Guangdong Medical College, Shenzhen 518033, Guangdong, CHINA; 3. Guangzhou Institute of Respiratory Diseases
(State Key Laboratory of Respiratory Diseases), Guangzhou 510120, Guangdong, CHINA

【Abstract】 Objective To determine the key activator protein-1 (AP-1) subunit involved in the characteris-
tics of the pathophysiology of asthma, in order to provide more accurate and novel molecular targets for the treatment
of asthma. Methods Asthmatic rat models were employed. One hundred and thirty Wistar male rats were randomly
divided into normal control, blank control, c-Jun antisense oligodeoxynucleotides (AS-ODNs), JunB AS-ODNs, JunD
AS-ODNs, c-Fos AS-ODNs, FosB AS-ODNs, Fra-1 AS-ODNs, Fra-2 AS-ODNs, and nonsense ODNs groups. After
gene silencing, the percentages of eosinophils (EOS) in the bronchoalveolar lavage fluid were calculated using haema-
toxylin-eosin staining, and interleukin (IL)-5 mRNA was detected by reverse transcription-polymerase chain reaction
(RT-PCR). Results The percentage of EOS in JunB AS-ODNs group was decreased significantly as compared with
that in the blank control [(34.33±9.62)% vs (13.39±3.72)%, P<0.001], but was still higher than that in the normal con-
trol [(5.61±1.76)%, P=0.04]. No significant differences in the percentages of EOS between other ODNs groups and
the blank control were observed (P>0.05). Compared with that in the blank control, the expression of IL-5 mRNA in
JunB AS-ODNs group was markedly suppressed [(0.554 2 ± 0.082 9) vs (0.822 4 ± 0.066 0), P<0.001], which was al-
so still higher than that in the normal control [(0.323 7±0.057 7), P<0.001]. There were no significant differences in
the expression of IL-5 mRNA between other ODNs groups and the blank control (P>0.05). Conclusion Chronic air-
way inflammation in asthmatic rats might depend on JunB, one of the subunits in the family of transcription factor
AP-1. JunB might be a novel therapeutic target in asthma.

      【Key words】 Activator protein-1 (AP-1); Subunits; Antisense oligodeoxynucleotides; Bronchial asthma
基金项目：广东省医学科学技术研究基金(编号：A2009621)；深圳市科技计划重点项目(编号：200901023)、福田区公益性科研项目(编号：
FTWS201040)