[1]李华君,唐小林,李洋,等.布地奈德通过调节IL-4/IL-13/STAT6影响大鼠黏膜重塑[J].第三军医大学学报,2018,40(12):1085-1090.
 LI Huajun,TANG Xiaolin,LI Yang,et al.Budesonide suppresses nasal mucosal remodeling by regulating IL-4/IL-13/STAT6 pathway in rats with allergic rhinitis[J].J Third Mil Med Univ,2018,40(12):1085-1090.
点击复制

布地奈德通过调节IL-4/IL-13/STAT6影响大鼠黏膜重塑(/HTML )
分享到:

《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
40卷
期数:
2018年第12期
页码:
1085-1090
栏目:
基础医学
出版日期:
2018-06-30

文章信息/Info

Title:
Budesonide suppresses nasal mucosal remodeling by regulating IL-4/IL-13/STAT6 pathway in rats with allergic rhinitis
作者:
李华君唐小林李洋余菲贾立峰袁伟
陆军军医大学(第三军医大学)第一附属医院耳鼻咽喉-头颈外科
Author(s):

budesonide; allergic rhinitis; interleukin-4; interleukin-13; STAT6; liquid chip; rats

关键词:
 
Keywords:
 
分类号:
R765.21;R967;R987
文献标志码:
A
摘要:

目的探讨布地奈德通过IL4/IL13/STAT6信号通路对变应性鼻炎(allergic rhinitis,AR)大鼠鼻黏膜重塑的影响。方法102只大鼠采用随机数字表法分为3组:空白组、ARPBS组、AR布地奈德组,每组34只。ARPBS组及AR布地奈德组大鼠为建模组大鼠,均采用卵清蛋白致敏的方法构建AR模型。建模成功后,使用微量移液枪双侧滴鼻治疗。ARPBS组给予(PBS)治疗,AR布地奈德组给予布地奈德(倍受您)治疗,空白组大鼠给予等量PBS治疗,治疗时间持续7 d。采用动物评价量表对各组大鼠行为学进行评分;ELISA法测定血清组胺(His)及IgE;液相芯片法测定血清及肺泡灌洗液IL4、IL13浓度;定量PCR检测STAT6基因表达,Western blot检测鼻黏膜总STAT6及磷酸化pSTAT6蛋白表达;鼻中隔黏膜HE染色及透射电镜扫描观察鼻黏膜重塑情况;采用SPSS 23.0统计软件对数据进行分析处理。结果建模组大鼠建模结束时动物行为学评分均>5分,血清His、IgE,血清及肺泡灌洗液IL4及IL13浓度以及鼻中隔黏膜STAT6及pSTAT6表达均显著高于空白组(P<0.01)。建模组大鼠采用不同方法治疗,AR布地奈德组干预7 d后,血清His、IgE,血清及肺泡灌洗液IL4、IL13浓度,以及鼻中隔黏膜STAT6、pSTAT6表达均下调,显著低于ARPBS组,差异有统计学意义(P<0.01)。HE染色及透射电镜结果显示建模组大鼠建模结束时鼻纤毛减少,布地奈德治疗后纤毛具有一定程度的恢复,治疗前后细胞连接无显著差异。结论布地奈德通过降低IL4、IL13、pSTAT6从而改善AR大鼠鼻黏膜症状。

Abstract:

ObjectiveTo investigate the effect of budesonide on nasal mucosal remodeling and the role of IL4/IL13/STAT6 signaling pathway in mediating this effect in rats with allergic rhinitis (AR). MethodsA total of 102 rats were randomly allocated into 3 equal groups, namely ARPBS group, ARbudesonide group and blank group. The rats in ARPBS and ARbudesonide groups were sensitized by challenges with ovalbumin to establish models of AR, and were subsequently treated by daily intranasal instillation with PBS and budesonide with aid of Eppendof for 7 consecutive days, respectively. The rats in the blank group were not challenged with ovalbumin and were treated with PBS in the same manner. Animal Assessment Scale was used to assess the behavioral changes of the rats after the treatments. Enzymelinked immunosorbent assay (ELISA) was used to detect the serum levels of histamine (His) and IgE, and the levels of interleukin (IL)13 and IL4 in the serum and bronchoalveolar lavage were analyzed with a Luminex liquid chip. STAT6 mRNA expression in the nasal mucosal was assessed with qPCR, and the protein expression levels of STAT6 and PSTAT6 were tested with Western blotting. HE staining and transmission electron microscopy were used to assess nasal septum remodeling after the treatments. ResultsThe rat models of AR all had a behavioral assessment score over 5 by the Animal Assessment Scale. Compared with those in the blank group, the rats with AR showed significantly increased serum levels of His and IgE, increased levels of IL13 and IL4 in both the serum and bronchoalveolar lavage, and also increased expression of STAT6 and PSTAT6 in the nasal mucosa (P<0.01). Budesonide treatment of the rats with AR for 7 days obviously lowered the serum levels of His and IgE, which remained unchanged in rats with PBS treatment. Compared with PBS treatment, budesonide treatment also decreased the levels of IL4 and IL13 in the serum and bronchoalveolar lavage and downregulated the expression of STAT6 and PSTAT6 in the nasal mucosa (P<0.01). HE staining and transmission electron microscopy showed that budesonide treatment partially reversed ARinduced reduction of nasal cilia in the rats without causing obvious changes in cell connection. ConclusionBudesonide improves the pathologies in the nasal mucosa of rats with AR by inhibiting IL4, IL13, and pSTAT6.

参考文献/References:

 
[1]DYKEWICZ M S, WALLACE D V, BAROODY F, et al. Treatment of seasonal allergic rhinitis: an evidencebased focused 2017 guideline update[J]. Ann Allergy Asthma Immunol, 2017,119(6): 489-511.e41. DOI: 10.1016/j.anai. 2017.08.012.
[2]RANGAMUWA K B, YOUNG A C, THIEN F. An epidemic of thunderstorm asthma in melbourne 2016: asthma, rhinitis, and other previous allergies[J]. Asia Pac Allergy, 2017,7(4): 193-198. DOI: 10.5415/apallergy.2017.7.4.193.
[3]YU S, HAN B, LIU S, et al. Derp1modified dendritic cells attenuate allergic inflammation by regulating the development of T helper type1(Th1)/Th2 cells and regulatory T cells in a murine model of allergic rhinitis[J]. Mol Immunol, 2017, 90: 172-181. DOI: 10.1016/j.molimm.2017. 07.015.
[4]MAY J R, DOLEN W K. Management of allergic rhinitis: a review for the community pharmacist[J]. Clin Ther, 2017, 39(12): 2410-2419. DOI: 10.1016/j.clinthera.2017.10. 006.
[5]LEE H J, KIM B, IM N R, et al. Decreased expression of Ecadherin and ZO1 in the nasal mucosa of patients with allergic rhinitis: altered regulation of Ecadherin by IL4, IL5, and TNFalpha[J]. Am J Rhinol Allergy, 2016, 30(3): 173-178. DOI: 10.2500/ajra.2016.30.4295.
[6]BARIK S, MILLER M M, CATTINROY A N, et al. IL4/IL13 signaling inhibits the potential of early thymic progenitors to commit to the T cell lineage[J]. J Immunol, 2017,199(8): 2767-2776. DOI: 10.4049/jimmunol.1700498.
[7]SUN L, REN X, WANG I C, et al. The FOXM1 inhibitor RCM1 suppresses goblet cell metaplasia and prevents IL13 and STAT6 signaling in allergenexposed mice[J]. Sci Signal, 2017,10(475): eaai8583. DOI: 10.1126/scisignal.aai8583.
[8]HOSOYA K, SATOH T, YAMAMOTO Y, et al. Gene silencing of STAT6 with siRNA ameliorates contact hypersensitivity and allergic rhinitis[J]. Allergy, 2011, 66(1): 124-131. DOI: 10.1111/j.13989995.2010.02440. x.
[9]RICCIO A M, TOSCA M A, COSENTINO C, et al. Cytokine pattern in allergic and nonallergic chronic rhinosinusitis in asthmatic children[J]. Clin Exp Allergy, 2002, 32(3): 422-426. 
[10]GHARIB ALY M A, EL TABBAKH M T, HEISSAM W F, et al. The study of a possible correlation between serum levels of interleukin 17 and clinical severity in patients with allergic rhinitis[J]. Allergy Rhinol (Providence), 2017, 8(3): e126-e131. DOI: 10.2500/ar.2017.8.0207.
[11]PARULEKAR A D, KAO C C, DIAMANT Z, et al. Targeting the interleukin4 and interleukin13 pathways in severe asthma: current knowledge and future needs[J]. Curr Opin Pulm Med, 2018,24(1): 50-55. DOI: 10.1097/MCP. 0000000000000436.
[12] 赵秀杰, 董震, 杨占泉, 等. 鼻超敏反应实验模型的建立[J]. 中华耳鼻咽喉科杂志, 1993, 28(1): 17-18.
ZHAO X J, DONG Z,YANG Z Q, et al. Establishment of experimental model of nasal hypersensitivity[J]. Chin J Otorhinolaryngol Head Neck Surg, 1993, 28(1): 17-18.

相似文献/References:

[1]钱迪,洪苏玲,杨玉成,等.我国西部部分地区变应性鼻炎流行病学抽样调查[J].第三军医大学学报,2008,30(06):539.
 QIAN Di,HONG Su-ling,YANG Yu-cheng,et al.Survey on epidemiological features of allergic rhinitis in western areas of China[J].J Third Mil Med Univ,2008,30(12):539.
[2]王建良,马晓菊.生物共振诊断治疗仪检测变应性鼻炎变应原的初步评估[J].第三军医大学学报,2011,33(15):1653.
[3]杨玉成,洪苏玲,黄江菊,等.卡介苗多糖核酸对变应性鼻炎病人Th1/Th2失衡状态的调节[J].第三军医大学学报,2005,27(12):1279.
[4]陈红江,高明华,李劲松,等.鼻内镜下聚焦超声治疗变应性鼻炎的临床应用[J].第三军医大学学报,2012,34(13):1350.
 Chen Hongjiang,Gao Minghua,Li Jinsong,et al.Focused ultrasound under nasal endoscopy in treatment of perennial allergic rhinitis[J].J Third Mil Med Univ,2012,34(12):1350.
[5]杨东宝,梁小军,李丽萍.变应性鼻炎合并鼻腔解剖结构异常50例[J].第三军医大学学报,2012,34(14):1437.
[6]陈红江,高明华,邹帆,等.特异益生菌株对变应性鼻炎患者的免疫调节作用[J].第三军医大学学报,2015,37(02):154.
 Chen Hongjiang,Gao Minghua,Zou Fan,et al.Immunomodulation effect of specific probiotics in allergic rhinitis patients[J].J Third Mil Med Univ,2015,37(12):154.
[7]朱瑾,吴军,易绍萱,等.腺病毒载体介导CTLA4Ig基因治疗小鼠变应性鼻炎[J].第三军医大学学报,2002,24(04):0.[doi:10.16016/j.1000-5404.2002.04.016 ]
 ZHU Jin,WU Jun,YI Shao xuan,et al.[J].J Third Mil Med Univ,2002,24(12):0.[doi:10.16016/j.1000-5404.2002.04.016 ]
[8]镡旭民,邓安春,杨桦,等.鼻内结构正常化手术对变应性鼻炎的治疗作用[J].第三军医大学学报,2000,22(07):0.[doi:10.16016/j.1000-5404.2000.07.034 ]
 CHAN Xu min,DEN An chun,YANG Hua,et al.[J].J Third Mil Med Univ,2000,22(12):0.[doi:10.16016/j.1000-5404.2000.07.034 ]

更新日期/Last Update: 2018-07-03