山东大学耳鼻喉眼学报 ›› 2022, Vol. 36 ›› Issue (3): 254-259.doi: 10.6040/j.issn.1673-3770.0.2021.174

• 临床研究 • 上一篇    下一篇

MAPK、PI3K-AKT、NF-κB在小鼠过敏性鼻炎中的表达及意义

张雅琪1,刘慧敏1,曹淋曼1,王子钰1,林旭1,李燕萍2,薛刚2,吴靖芳2   

  1. 1. 河北北方学院基础医学院, 河北 张家口 075000;
    2. 河北省张家口市甲状腺癌精准诊疗重点实验室, 河北 张家口 075000
  • 发布日期:2022-06-15
  • 通讯作者: 薛刚. E-mail:xgwjf@163.com;吴靖芳. E-mail:641426737@qq.com
  • 基金资助:
    河北北方学院大学生创新创业计划项目(xj201957);张家口市科技计划(2021001A)

Expression and significance of the MAPK,PI3K-AKT,NF-κB pathways of allergic rhinitis in mice

ZHANG Yaqi1, LIU Huimin1, CAO Linman1, WANG Ziyu1, LIN Xu1, LI Yanping2, XUE Gang2, WU Jingfang2   

  1. 1. School of Basic Medicine, Hebei North University, Zhangjiakou, 075700, Hebei, China;
    2. Key Laboratory for Accurate Diagnosis and Treatment of Thyroid Cancer, Zhangjiakou, 075700, Hebei, China
  • Published:2022-06-15

摘要: 目的 通过构建小鼠过敏性鼻炎模型探讨多信号通路蛋白在过敏性鼻炎发生发展中的机制。 方法 40只昆明小鼠随机分为过敏性鼻炎组和对照组(每组20只)。分离两组小鼠头部各8只,4%多聚甲醛固定、石蜡包埋、切片、HE染色法观察小鼠鼻黏膜病理改变、免疫组化检测MAPK、NF-κB、PI3K-AKT信号通路蛋白的表达,24只小鼠鼻黏膜蛋白用于Western blotting分析。 结果 过敏性鼻炎组小鼠的抓挠、喷嚏、流鼻涕等均远多于对照组,差异具有统计学意义(P<0.05);HE染色过敏性鼻炎组黏膜出现假复层纤毛柱状上皮坏死,上皮结构重构,嗜酸性粒细胞浸润等典型鼻炎病理改变。过敏性鼻炎组三条通路关键蛋白的免疫阳性信号AOD值不同程度的高于对照组(P<0.05)。Western blotting结果显示过敏性鼻炎组与对照组相比MAPK、PI3K-AKT、NF-κB三条信号通路蛋白表达升高,差异有统计学意义(P<0.05)。 结论 在小鼠过敏性鼻炎发病过程中MAPK、NF-κB、PI3K-AKT三条信号通路蛋白的表达均升高,其激活在小鼠过敏性鼻炎过程中可能存在协同效应。

关键词: 多条信号通路, 过敏性鼻炎, MAPK, AKT, NF-κB

Abstract: Objective To explore the mechanism of multi-signaling pathways proteins in the development of allergic rhinitis(AR)in mice. Methods Forty Kunming mice were randomly divided into allergic rhinitis group(AR group)and control group(Con group)each 20 mice. The nasal of 8 mice in each group was fixed with 4% paraformaldehyde, embedded in paraffin, sectioned and stained by HE method to observe the pathological changes of nasal mucosa. And the expression of MAPK, NF-κB and PI3K-AKT pathways proteins were detected by immunohistochemistry(IHC). The other 24 mice of each group were prepared for Western blot(WB)analysis. Results The behavioral results showed that scratching, sneezing and runny nose of the AR group were far more than Con group(P<0.05). In the HE staining, the mucosa showed pseudostratified ciliated columnar epithelial necrosis, epithelial structural remodeling and eosinophil infiltration etc. typical pathological changes of rhinitis. IHC showed that the positive proteins of three key pathways in the AR group was higher than that of the Con group. The proteins expression of MAPK, PI3K-AKT and NF-κB in the AR group were increased compared with the Con group and had a significant differences by western blot(P<0.05). Conclusion The increased proteins of MAPK, NF-κB and PI3K-AKT signaling pathways may have a synergistic effect on the pathogenesis of AR in mice.

Key words: Multiple signaling pathways, Allergic rhinitis, MAPK, AKT, NF-κB

中图分类号: 

  • R765.21
[1] May JR, Dolen WK. 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.
[2] 倪璟滋,万文锦,程雷.变应性鼻炎健康相关生活质量研究进展[J].山东大学耳鼻喉眼学报,2022, 36(3)110-115. doi:10.6040/j.issn.16733770.1.2021.165. NI Jingzi, WANG Wenjin, CHENG Lei. Research progress on health-related quality of life in allergic rhinitis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(3)110-115. doi:10.6040/j.issn.16733770.1.2021.165.
[3] Passali D, Passali GC, Damiani V, et al. The impact of Allergic Rhinitis in clinical practice: an International Survey[J]. J Biol Regul Homeost Agents, 2021, 35(1 Suppl. 2): 39-43. doi:10.23812/21-1supp2-8.
[4] 王孟, 郑铭, 王向东, 等. 中国过敏性鼻炎流行病学研究进展[J]. 中国耳鼻咽喉头颈外科, 2019, 26(8): 415-420. doi:10.16066/j.1672-7002.2019.08.004. WANG Meng, ZHENG Ming, WANG Xiangdong, et al. Progress in epidemiology of allergic rhinitis in China[J]. Chinese Archives of Otolaryngology-Head and Neck Surgery, 2019, 26(8): 415-420. doi:10.16066/j.1672-7002.2019.08.004.
[5] 程雷,周文成,陆美萍. 中国变应性鼻炎和哮喘舌下免疫治疗指南英文版精要解读[J]. 临床耳鼻咽喉头颈外科杂志,2020, 34(4):292-295. doi:10.13201/j.issn.2096-7993.2020.04.002。 CHENG Lei, ZHOU Wencheng, LU Meiping. Highlights of the Chinese guideline on sublingual immunotherapy for allergic rhinitis and asthma(English edition)[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2020, 34(4): 292-295. doi:10.13201/j.issn.2096-7993.2020.04.002.
[6] 王成硕,王向东,张罗.《变应性鼻炎及其对哮喘的影响(ARIA)》指南2016年修订版解读[J].中华耳鼻咽喉头颈外科杂志,2018,53(10):798-800. doi: 10.13201/j.issn.1001-1781.2017.17.007.
[7] 乔菁, 杨扬, 余咏梅. 变应性鼻炎机制研究和治疗的新进展[J]. 中国医学文摘(耳鼻咽喉科学), 2021, 36(1): 166-168, 188. doi:10.19617/j.issn1001-1307.2021.01.166. QIAO Jing, YANG Yang, YU Yongmei. Recent advances in pathogenesis and medicine of allergic rhinitis[J]. Chinese Medical Digest(Otorhinolaryngology), 2021, 36(1): 166-168, 188. doi:10.19617/j.issn1001-1307.2021.01.166.
[8] Shao JB, Luo XQ, Mo LH, et al. Twist1 sustains the apoptosis resistance in eosinophils in nasal mucosa of allergic rhinitis[J]. Arch Biochem Biophys, 2021, 702: 108828. doi:10.1016/j.abb.2021.108828.
[9] Qiao Y, Chen J. Investigating the inflammatory cascade effect of basophil activation in children with allergic rhinitis or asthma, via the IgE-FcεRI-NF-κB signaling pathway[J]. Adv Clin Exp Med, 2021, 30(7): 673-679. doi:10.17219/acem/135756.
[10] Fu SL, Ni SH, Wang DN, et al. Coptisine suppresses mast cell degranulation and ovalbumin-induced allergic rhinitis[J]. Molecules, 2018, 23(11): 3039. doi:10.3390/molecules23113039.
[11] 苗明三, 项丽玲, 苗艳艳. 变应性鼻炎动物模型制备规范(草案)[J]. 中草药, 2018, 49(1): 50-57. MIAO Mingsan, XIANG Liling, MIAO Yanyan. Specification for preparation of allergic rhinitis animal model(draft)[J]. Chinese Traditional and Herbal Drugs, 2018, 49(1): 50-57.
[12] 蔺林, 严文洪, 赵霞. 氢氧化铝佐剂对变应性鼻炎小鼠模型的影响[J]. 临床耳鼻咽喉头颈外科杂志, 2014, 28(11): 780-784. doi:10.13201/j.issn.1001-1781.2014.11.008. LIN Lin, YAN Wenhong, ZHAO Xia. Influence of aluminum hydroxide adjuvant on a murine model of allergic rhinitis[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2014, 28(11): 780-784. doi:10.13201/j.issn.1001-1781.2014.11.008.
[13] 张普文. CD23在嗜酸粒细胞性慢性鼻窦炎伴鼻息肉发病机制中的作用[D]. 郑州: 郑州大学, 2020.
[14] 孙天一. 朝医方麻黄定喘汤通过调控NF-κB、MAPK信号通路改善哮喘小鼠气道重塑的机制研究[D]. 延吉: 延边大学, 2019.
[15] Kwak S, Choi YS, Na HG, et al. Benzisothiazolinone upregulates the MUC5AC expression via ERK1/2, p38, and NF-κB pathways in airway epithelial cells[J]. Toxicol Res(Camb), 2019, 8(5): 704-710. doi:10.1039/c9tx00135b.
[16] 欧阳昱晖, 范尔钟, 李颖, 等. 水通道蛋白5在过敏性鼻炎黏膜过度表达及其对腺体分泌的影响[J]. 中国耳鼻咽喉头颈外科, 2018, 25(9): 503-506. doi:10.16066/j.1672-7002.2018.09.011. OUYANG Yuhui, FAN Erzhong, LI Ying, et al. Overexpression of aquaporin 5 in nasal mucosa of allergic rhinitis patients and its effect on glandular secretion[J]. Chinese Archives of Otolaryngology-Head and Neck Surgery, 2018, 25(9): 503-506. doi:10.16066/j.1672-7002.2018.09.011.
[17] 刘成, 卫平存, 胡金旺, 等. 18β-甘草次酸对变应性鼻炎大鼠鼻黏膜中水通道蛋白5及黏蛋白5AC的影响[J]. 中国耳鼻咽喉头颈外科, 2020, 27(7): 398-403. doi:10.16066/j.1672-7002.2020.07.009. LIU Cheng, WEI Pingcun, HU Jinwang, et al. Effect of 18β-glycyrrhetinic acid on the expression of AQP5 and MUC5AC in the nasal mucosa of allergic rhinitis rats[J]. Chinese Archives of Otolaryngology-Head and Neck Surgery, 2020, 27(7): 398-403. doi:10.16066/j.1672-7002.2020.07.009.
[18] Li HX, Guo DD, Zhang LR, et al. Glycyrrhizin attenuates histamine-mediated MUC5AC upregulation, inflammatory cytokine production, and aquaporin 5 downregulation through suppressing the NF-κB pathway in human nasal epithelial cells[J]. Chem Biol Interact, 2018, 285: 21-26. doi:10.1016/j.cbi.2018.02.010.
[19] Lin WL, Su FS, Gautam R, et al. Raf kinase inhibitor protein negatively regulates FcεRI-mediated mast cell activation and allergic response[J]. Proc Natl Acad Sci USA, 2018, 115(42): E9859-E9868. doi:10.1073/pnas.1805474115.
[20] Sun YZ, Yang YL, Zhao Y, et al. The role of the tyrosine kinase Lyn in allergy and cancer[J]. Mol Immunol, 2021, 131: 121-126. doi:10.1016/j.molimm.2020.12.028.
[21] 郑文雅. 肥大细胞FcεRⅠ受体介导的信号通路分子机制及影响因素的研究进展[J]. 医学研究生学报, 2021, 34(6): 646-652. doi:10.16571/j.cnki.1008-8199.2021.06.016. ZHENG Wenya. Advances in molecular mechanisms and affecting factors of FcεRI receptor-mediated signaling pathways in mast cell[J]. Journal of Medical Postgraduates, 2021, 34(6): 646-652. doi:10.16571/j.cnki.1008-8199.2021.06.016.
[1] 杜康丽,郑振宇,徐战将,张宇,陈露,卢梦垚. 鼻中隔偏曲并发慢性鼻窦炎风险预测模型的构建与验证[J]. 山东大学耳鼻喉眼学报, 2025, 39(6): 78-86.
[2] 黄焕,华红利,邓玉琴,江承洋,王雨薇,杨星海. 儿童过敏性鼻炎、扁桃体腺样体肥大和鼻窦炎之间相关性及其对临床指导价值[J]. 山东大学耳鼻喉眼学报, 2025, 39(5): 34-41.
[3] 张杰,陈敏,申征征,吴宇华,刘原虎,孙浩,谭新华,倪树仁,杨书勋,史雪峥,倪鑫. 过敏性鼻炎与儿童新冠病毒肺炎感染及症状的关联性研究[J]. 山东大学耳鼻喉眼学报, 2024, 38(4): 36-42.
[4] 张真,杨卓莹,周佳妮,张大为,陈仁杰. 环索奈德鼻喷剂治疗季节性过敏性鼻炎疗效与安全的Meta分析[J]. 山东大学耳鼻喉眼学报, 2024, 38(1): 13-20.
[5] 乌日柴夫,苏日古格,孟永梅. 卵清蛋白诱导的过敏性鼻炎豚鼠模型的建立与评价及蒙医舌尿诊的初步分析[J]. 山东大学耳鼻喉眼学报, 2024, 38(1): 32-38.
[6] 王剑,杜伟嘉,薛涛,陈福权. 利用百度指数分析中国过敏性鼻炎及相关变应性疾病的流行特征[J]. 山东大学耳鼻喉眼学报, 2023, 37(5): 31-41.
[7] 王晓嫒,张欠欠,程翔宇,李志鹏,张维天,叶海波. 翼管神经切断术治疗2型慢性鼻窦炎伴过敏性鼻炎的临床疗效分析[J]. 山东大学耳鼻喉眼学报, 2023, 37(5): 42-49.
[8] 毕晓云,马本绪,王心茹,李旭豪,杨继国. 穴位贴敷治疗小儿过敏性鼻炎随机对照试验的Meta分析[J]. 山东大学耳鼻喉眼学报, 2023, 37(4): 75-85.
[9] 王惟一,时蕾,张志玉,张贵玲,时光刚. 高脂饮食对过敏性鼻炎小鼠致敏影响和肠道菌群改变的研究[J]. 山东大学耳鼻喉眼学报, 2023, 37(3): 21-29.
[10] 孙娜,黄昱,章如新,张雪琰,牛越,段玉森,阚海东. 臭氧对变应性鼻炎鼻黏膜NF-κB p65核蛋白表达及炎性因子的影响[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 237-244.
[11] 庞冲,边赛男,张冰,尹旭,陆颖霞,叶鹏飞,王湛,赵晶,高彦,关凯. 儿童过敏性鼻炎粉尘螨特异性舌下免疫治疗短期疗效评估[J]. 山东大学耳鼻喉眼学报, 2022, 36(1): 70-74.
[12] 王鑫,刘巧平,闫占峰,刘思溟,朱雅静,丁倩,张莹,田媛,张京然. 基于网络药理学探究小青龙汤治疗过敏性鼻炎的作用机制[J]. 山东大学耳鼻喉眼学报, 2021, 35(5): 46-55.
[13] 王宇婷,王嘉玺. microRNA在过敏性鼻炎发病机制中的研究进展[J]. 山东大学耳鼻喉眼学报, 2021, 35(5): 98-104.
[14] 李化静,郝润梅,戴皓,张令,申震,权芳,邵渊. 儿茶素抑制卵清蛋白诱导的过敏性鼻炎小鼠模型炎症反应的机制研究[J]. 山东大学耳鼻喉眼学报, 2021, 35(4): 1-7.
[15] 林兴,沈翎,林宗通,杨中婕. 儿童鼻腔异物与过敏性鼻炎关系的初步研究[J]. 山东大学耳鼻喉眼学报, 2020, 34(4): 101-104.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!