Effects of <italic style="font-style: italic">Bimin Formula </italic>（鼻敏方） on the Nasal Mucosa TMEM16A/NF-κB/MUC5AC Signaling Pathway in a Rat Model of Allergic Rhinitis with Lung-Spleen <italic style="font-style: italic">Qi</italic> Deficiency

XU Ningcong; HUA Yiwei; TAN Xi; WANG Jinhan; LIANG Zihua; ZHOU Shiqing; LI Yunying; CHEN Wenyong; XIA Jiyan; LUO Qiulan

doi:10.13288/j.11-2166/r.2024.08.012

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Effects of Bimin Formula （鼻敏方） on the Nasal Mucosa TMEM16A/NF-κB/MUC5AC Signaling Pathway in a Rat Model of Allergic Rhinitis with Lung-Spleen Qi Deficiency

更新时间：2024-04-11

- Effects of Bimin Formula （鼻敏方） on the Nasal Mucosa TMEM16A/NF-κB/MUC5AC Signaling Pathway in a Rat Model of Allergic Rhinitis with Lung-Spleen Qi Deficiency
- Journal of Traditional Chinese Medicine Vol. 65, Issue 8, Pages: 842-848(2024)
- 作者机构：
  
  1.广州中医药大学第二临床医学院，广东省广州市白云区机场路12号，510405
  2.广州中医药大学第二附属医院
  3.广州中医药大学中药学院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2024.08.012
  CLC：
- Received：17 October 2023，
  
  Revised：2023-12-15，
  
  Published：17 April 2024
- 稿件说明：
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徐宁聪,画奕惟,谭希等.鼻敏方对变应性鼻炎肺脾气虚证模型大鼠鼻黏膜TMEM16A/NF-κB/MUC5AC信号通路的影响[J].中医杂志,2024,65(08):842-848.

XU Ningcong,HUA Yiwei,TAN Xi,et al.Effects of Bimin Formula （鼻敏方） on the Nasal Mucosa TMEM16A/NF-κB/MUC5AC Signaling Pathway in a Rat Model of Allergic Rhinitis with Lung-Spleen Qi Deficiency[J].Journal of Traditional Chinese Medicine,2024,65(08):842-848.
徐宁聪,画奕惟,谭希等.鼻敏方对变应性鼻炎肺脾气虚证模型大鼠鼻黏膜TMEM16A/NF-κB/MUC5AC信号通路的影响[J].中医杂志,2024,65(08):842-848. DOI： 10.13288/j.11-2166/r.2024.08.012.

XU Ningcong,HUA Yiwei,TAN Xi,et al.Effects of Bimin Formula （鼻敏方） on the Nasal Mucosa TMEM16A/NF-κB/MUC5AC Signaling Pathway in a Rat Model of Allergic Rhinitis with Lung-Spleen Qi Deficiency[J].Journal of Traditional Chinese Medicine,2024,65(08):842-848. DOI： 10.13288/j.11-2166/r.2024.08.012.

摘要

目的

探讨鼻敏方治疗变应性鼻炎（AR）肺脾气虚证黏液高分泌的可能作用机制。

方法

34只SD大鼠随机分为空白组（8只）、模型组（8只）、鼻敏方低剂量组（8只）、鼻敏方高剂量组（10只）。除空白组外，其余各组大鼠以烟熏+番泻叶灌胃+卵清蛋白法建立AR肺脾气虚证大鼠模型。造模结束后，鼻敏方低、高剂量组大鼠分别给予鼻敏方浓缩液（浓度为2.16 g/ml）1.08 g/100 g、2.16 g/100 g灌胃，模型组给予0.5 ml/100 g生理盐水灌胃，均每日1次，持续28天；空白组不干预。干预后进行行为学评价，ELISA法检测大鼠外周血总免疫球蛋白E（IgE）水平，HE染色观察大鼠鼻上皮黏膜病理学变化，免疫组化法检测鼻上皮黏膜的跨膜蛋白16A（TMEM16A）、黏蛋白5AC（MUC5AC）蛋白表达，Western Blot法检测鼻上皮黏膜核转录因子κB（NF-κB）蛋白表达，RT-PCR法检测鼻上皮黏膜TMEM16A、MUC5AC、NF-κB mRNA表达。

结果

HE染色显示，空白组大鼠鼻上皮黏膜上皮细胞结构完整无脱落，无水肿、坏死等病变；模型组大鼠鼻上皮黏膜上皮组织增厚且部分脱落，可见嗜酸性粒细胞和淋巴细胞浸润；鼻敏方高、低剂量组大鼠鼻上皮黏膜组织病理均有改善，且鼻敏方高剂量组改善更明显。与空白组比较，模型组大鼠行为学积分及外周血总IgE水平显著升高，鼻上皮黏膜TMEM16A、MUC5AC、NF-κB蛋白及mRNA表达升高（

＜0.05或

＜0.01）。与模型组比较，鼻敏方高剂量组大鼠行为学积分及外周血总IgE水平降低，鼻上皮黏膜TMEM16A、MUC5AC、NF-κB蛋白及mRNA表达降低（

＜0.05或

＜0.01）；鼻敏方低剂量组大鼠行为学积分及外周血总IgE水平降低，鼻上皮黏膜TMEM16A、MUC5AC蛋白及mRNA表达降低，NF-κB蛋白表达降低（

＜0.05或

＜0.01），NF-κB mRNA表达差异无统计学意义（

＞0.05）。与鼻敏方低剂量组比较，鼻敏方高剂量组NF-κB蛋白表达降低（

＜0.01）。

结论

鼻敏方可能通过调控鼻上皮黏膜TMEM16A/NF-κB/MUC5AC信号通路改善AR肺脾气虚症状及黏液高分泌。

Abstract

Objective

To explore the possible mechanism of

Bimin Formula

（鼻敏方） in treating lung-spleen

deficiency syndrome of allergic rhinitis （AR） with high mucin secretion.

Methods

Thirty-four SD rats were randomly divided into a blank group （8 rats）， a model group （8 rats）， a low-dose

Bimin Formula

group （8 rats）， and a high-dose

Bimin Formula

group （10 rats）. Except for the blank group， the other groups were subjected to AR lung-spleen

deficiency rat models induced by smoking， gavage of Ginkgo biloba leaf extract， and ovalbumin. After modeling， rats in the low- and high-dose

Bimin Formula

groups were given

Bimin Formula

concentrate （concentration of 2.16 g/ml） by gavage at doses of 1.08 g/100 g and 2.16 g/100 g， respectively， while rats in the model group were given 0.5 ml/100 g of normal saline by gavage， once daily for 28 days； the blank group was not intervened. Behavioral assessments were performed after intervention. ELISA was used to detect the levels of peripheral blood total immunoglobulin E （IgE）. HE staining was used to observe the pathological changes of nasal mucosa epithelium in rats， while immunohistochemistry was used to detect the expression of transmembrane protein 16A （TMEM16A） and mucin 5AC （MUC5AC） protein in nasal mucosa. Western Blot was used to detect the expression of nuclear factor kappa B （NF-κB） protein， and RT-PCR was used to detect the expression of TMEM16A， MUC5AC， and NF-κB mRNA in nasal mucosa.

Results

HE staining showed that the nasal mucosa epithelial cell structure in the blank group was intact without shedding， swelling， or necrosis； the nasal mucosa epithelial tissue of rats in the model group was thickened and partially shed， with infiltration of eosinophils and lymphocytes visible； the pathological changes in nasal mucosa tissue of rats in the high- and low-dose

Bimin Formula

groups were improved， and more improvement was showen in the high-dose group. Compared with those in the blank group， the behavioral scores and peripheral blood total IgE levels of rats in the model group significantly increased， as well as the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosa （

＜0.05 or

＜0.01）. Compared with those in the model group， the behavioral scores and peripheral blood total IgE levels of rats in the high-dose

Bimin Formula

group decreased， and the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosaalso decreased （

＜0.05 or

＜0.01）； the behavioral scores and peripheral blood total IgE levels of rats in the low-dose

Bimin Formula

group were reduced， and the expression of TMEM16A and MUC5AC proteins and mRNA in nasal mucosa， as well as the expression of NF-κB protein decreased （

＜0.05 or

＜0.01）， but the difference in NF-κB mRNA expression was not statistically significant （

＞0.05）. Compared with the low-dose

Bimin Formula

group， the expression of NF-κB protein in the high-dose group decreased （

＜0.01）.

Conclusion

Bimin Formula

may improve the symptoms and high mucus secretion of AR lung-spleen

deficiency by regulating the TMEM16A/NF-κB/MUC5AC signaling pathway in nasalmucosa.

关键词

Keywords

references

中华耳鼻咽喉头颈外科杂志编辑委员会鼻科组，中华医学会耳鼻咽喉头颈外科学分会鼻科学组 . 中国变应性鼻炎诊断和治疗指南（2022年，修订版）［J］. 中华耳鼻咽喉头颈外科杂志， 2022 ， 57 （ 2 ）： 106 - 129 .

BROŻEK JL ， BOUSQUET J ， AGACHE I ， et al . Allergic rhinitis and its impact on asthma （ARIA） guidelines：2016 revision ［J］. J Allergy Clin Immunol ， 2017 ， 140 （ 4 ）： 950 - 958 .

阮岩 . 中医耳鼻咽喉科学［M］. 北京：人民卫生出版社， 2012 ： 133 - 136 .

史军，刘玉 . 1710例变应性鼻炎患者中医辨证分型调查分析［J］. 辽宁中医药大学学报， 2017 ， 19 （ 10 ）： 42 - 44 .

李云英，薛长利 . 中医药临床循证丛书（第一辑）：变应性鼻炎［M］. 北京：人民卫生出版社， 2019 ： 31-46，56-88 .

李晓珊 . “培土生金”法干预变应性鼻炎随机双盲对照临床研究［D］. 广州：广州中医药大学， 2018 .

冯小聪，黄唯，周世卿，等 . 鼻敏方通过NF-κB信号通路对肺脾气虚变应性鼻炎大鼠鼻黏膜水通道蛋白5的影响［J］. 中国实验方剂学杂志， 2020 ， 26 （ 8 ）： 81 - 88 .

EVANS CM ， RACLAWSKA DS ， TTOFALI F ， et al . The polymeric mucin Muc5ac is required for allergic airway hyperreactivity ［J］. Nat Commun ， 2015 ， 6 ： 6281 . doi： 10. 1038/ncomms7281 http://dx.doi.org/10.1038/ncomms7281 .

张涛，王向东，张罗 . 跨膜蛋白16A在呼吸道黏膜上皮细胞的表达和功能研究［J］. 国际耳鼻咽喉头颈外科杂志， 2018 ， 42 （ 2 ）： 67 - 72 .

LIN J ， JIANG Y ， LI L ， et al . TMEM16A mediates the hypersecretion of mucus induced by Interleukin-13 ［J］. Exp Cell Res ， 2015 ， 334 （ 2 ）： 260 - 269 .

陈小野，艾景录，吕爱平，等 . 实用中医证候动物模型学［M］. 北京：北京医科大学中国协和医科大学联合出版社， 1993 .

赵金铎，张镜人，张震，等 . 中医证候鉴别诊断学［M］. 北京：人民卫生出版社， 1987 ： 173 - 175 .

黄唯，冯小聪，周世卿，等 . 肺脾气虚证变应性鼻炎大鼠模型的建立及评价［J］. 时珍国医国药， 2020 ， 31 （ 6 ）： 1502 - 1505 .

YANG YD ， CHO H ， KOO JY ， et al . TMEM16A confers receptor-activated calcium-dependent chloride conductance ［J］. Nature ， 2008 ， 455 （ 7217 ）： 1210 - 1215 .

SCHROEDER BC ， CHENG T ， JAN YN ， et al . Expression cloning of TMEM16A as a calcium-activated chloride channel subunit ［J］. Cell ， 2008 ， 134 （ 6 ）： 1019 - 1029 .

KANG JW ， LEE YH ， KANG MJ ， et al . Synergistic mucus secretion by histamine and IL-4 through TMEM16A in airway epithelium ［J］. Am J Physiol Lung Cell Mol Physiol ， 2017 ， 313 （ 3 ）： 466 - 476 .

WANG W ， ZHENG M . Mucin 5 subtype AC expression and upregulation in the nasal mucosa of allergic rhinitis rats ［J］. Otolaryngol Head Neck Surg ， 2012 ， 147 （ 6 ）： 1012 - 1019 .

RYU J ， KIM KI ， HOSSAIN R ， et al . Meclofenamate suppresses MUC5AC mucin gene expression by regulating the NF-κB signaling pathway in human pulmonary mucoepidermoid NCI-H292 cells ［J］. Biomol Ther （Seoul）， 2023 ， 31 （ 3 ）： 306 - 311 .

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Effects of Bimin Formula （鼻敏方） on the Nasal Mucosa TMEM16A/NF-κB/MUC5AC Signaling Pathway in a Rat Model of Allergic Rhinitis with Lung-Spleen Qi Deficiency

DOI：10.13288/j.11-2166/r.2024.08.012

摘要

Abstract

关键词

Keywords

references