固本防哮饮对哮喘缓解期小鼠气道杯状细胞增生与黏液分泌相关基因的调控作用

陆远; 赵霞

固本防哮饮对哮喘缓解期小鼠气道杯状细胞增生与黏液分泌相关基因的调控作用

陆远,
赵霞

江苏省儿童呼吸疾病中医药重点实验室，南京中医药大学中医儿科学研究所，江苏南京 210023

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出版历程
- 收稿日期: 2016-10-25
- 修回日期: 2017-01-05
- 刊出日期: 2017-03-10

Effects of Guben Fangxiao Decoction on the mRNA Expression of Genes Related to Airway Goblet Cell Hyperplasia and Mucus Hypersecretion in a Murine Asthma Remission Model

LU Yuan,
ZHAO Xia

摘要

摘要: 目的探讨中药复方固本防哮饮对哮喘缓解期小鼠气道杯状细胞增生与黏液分泌相关基因IRE1β、SPDEF、AGR2和mCLCA3的影响。方法结合前期研究采用卵蛋白(OVA)致敏和OVA-呼吸道合胞病毒(RSV)联合诱导激发BALB/c雌性小鼠，建立哮喘缓解期动物模型，随机分为正常组，模型组，固本防哮饮低、中、高剂量组，孟鲁司特钠组及地塞米松组。qPCR法检测肺组织中IRE1β、SPDEF、AGR2和mCLCA3 mRNA表达水平。结果模型组小鼠肺组织中IRE1β、SPDEF、AGR2 mRNA表达显著高于正常组(P＜0.05)，而mCLCA3 mRNA表达显著低于正常组(P＜0.05)；固本防哮饮高、中、低剂量组，孟鲁司特钠组及地塞米松组小鼠肺组织中IRE1β、SPDEF、AGR2 mRNA水平较模型组存在不同程度的下降，而固本防哮饮低剂量组和孟鲁司特钠组小鼠肺组织中mCLCA3 mRNA表达显著高于正常组(P＜0.05)。结论固本防哮饮防治哮喘抑制气道杯状细胞增生和减少黏液分泌的作用机制可能是通过降低IRE1β、SPDEF、AGR2 mRNA表达所致。
- 固本防哮饮 /
- 哮喘缓解期 /
- 气道 /
- 杯状细胞增生 /
- 黏液高分泌
Abstract: OBJECTIVE To investigate the effects of Guben Fangxiao Decoction on mRNA expression of airway goblet cells hyperplasia and mucus hypersecretion-associated genes like IRE1β， SPDEF， AGR2， and mCLCA3 in mice model with asthma at remission stage. METHODS Based on the previous study， OVA sensitization combined with RSV sensitization was applied to establish the asthma model on BALB/c female mice， which were randomly divided into the normal group， model group， Guben Fangxiao Decoction of low， middle and high dose groups， montelukast sodium group and dexamethasone group. qPCR was applied to detect the expression of IRE1β， SPDEF， AGR2 and mCLCA3 mRNA in the lung tissue. RESULTS The expressions of IRE1β， SPDEF and AGR2 mRNA in the lung tissue of the model group were significantly higher than those of the normal group(P<0.05)， while the mCLCA3 mRNA expression was much lower than the normal group(P<0.05). The mCLCA3 mRNA expressions in the lung tissue of Guben Fangxiao Decoction with low， middle and high dosage groups， montelukast sodium group and dexamethasone group experienced decline to different degree. Whereas the mCLCA3 mRNA levels in the Guben Fangxiao Decoction Low dose group and montelukast sodium group were significantly higher than those of the normal group(P<0.05). CONCLUSION Gubenfangxiao Decoction can significantly attenuate RSV-OVA-induced airway goblet cells hyperplasia and mucus hypersecretion in murine asthma remission model. These effects may be mediated， at least partially， by suppressing the mRNA expression of IRE1β， SPDEF and AGR2.
- Guben Fangxiao Decoction /
- asthma remission /
- airway /
- goblet cell hyperplasia /
- mucus hypersecretion

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参考文献(22)

[1]	Global Initiative for Asthma. Global strategy for asthma management and prevention[EB/OL]. http://www.ginasthma.org， 2014.
[2]	ROGERS DF. The airway goblet cell [J]. Int J Biochem Cell Biol， 2003， 35(1): 1-6.
[3]	ROGERS DF. Physiology of airway mucus secretion and pathophysiology of hypersecretion [J]. Respir Care， 2007， 52(9): 1134-1149.
[4]	ROGERS DF. Airway mucus hypersecretion in asthma: an undervalued pathology? [J]. Curr Opin Pharm， 2004， 4(3): 241-250.
[5]	ROGERS DF. Mucoactive agents for airway mucus hypersecretory diseases [J]. Respir Care， 2007， 52(9): 1176-1197.
[6]	袁雪晶，孙轶秋．固本防哮饮联合穴位敷贴治疗儿童哮喘缓解期100例临床研究 [J]．中华中医药杂志，2010，25(12)：2306-2309.
[7]	YUAN XJ， SUN YQ. Clinical research of Gubenfangxiao decoction combined with acupoint application on chronic asthmatic children in 100 cases [J]. China J Tradit Chin Med Pharm， 2010， 25(12)， 2306–2309.
[8]	HUANG Z， GAO L， ZHAO X， et al. Effect of Gubenfangxiao decoction on respiratory syncytial virus-induced asthma and expression of asthma susceptibility gene orosomucoid 1-like protein 3 in mice [J]. J Tradit Chin Med， 2016， 36(1): 101-106.
[9]	LU Y， XU JY， ZHANG XH， et al. Gu-Ben-Fang-Xiao decoction attenuates sustained airway inflammation by suppressing ER stress response in a murine asthma remission model of respiratory syncytial virus infection [J]. J Ethnopharmacol， 2016， 192: 496-509.
[10]	IWAWAKI T， HOSODA A， OKUDA T， et al. Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress [J]. Nat Cell Biol， 2001， 3(2): 158-164.
[11]	MARTINO MB， JONES L， BRIGHTON B， et al. The ER stress transducer IRE1β is required for airway epithelial mucin production [J]. Mucosal Immunol， 2013， 6(3): 639-654.
[12]	DAY A， CARLSON MR， DONG J， et al. Celsius: a community resource for Affymetrix microarray data [J]. Genom Biol， 2007， 8(6): 1.
[13]	HESSELINK AE， VAN DER WINDT DA， Penninx BW， et al. What predicts change in pulmonary function and quality of life in asthma or COPD? [J]. J Asthma， 2006， 43(7): 513-519.
[14]	ROGERS DF， EVANS TW. Plasma exudation and oedema in asthma [J]. Br Med Bull， 1992， 48(1): 120-134.
[15]	SHEEHAN JK， RICHARDSON PS， FUNG DC， et al. Analysis of respiratory mucus glycoproteins in asthma: a detailed study from a patient who died in status asthmaticus [J]. Am J Respir Cell Mol Biol， 1995， 13(6): 748-756.
[16]	LIST SJ， FINDLAY BP， FORSTNER GG， et al. Enhancement of the viscosity of mucin by serum albumin [J]. Biochem J， 1978， 175(2): 565-571.
[17]	LAI HY， ROGERS DF. Mucus hypersecretion in asthma: intracellular signalling pathways as targets for pharmacotherapy [J]. Curr Opin Aller Clin Immunol， 2010， 10(1): 67-76.
[18]	TSURU A， FUJIMOTO N， TAKAHASHI S， et al. Negative feedback by IRE1β optimizes mucin production in goblet cells [J]. Proc Nat Acad Sci， 2013， 110(8): 2864-2869.
[19]	KORFHAGEN TR， KITZMILLER J， CHEN G， et al. SAM-pointed domain ETS factor mediates epithelial cell–intrinsic innate immune signaling during airway mucous metaplasia [J]. Proc Nat Acad Sci， 2012， 109(41): 16630-16635.
[20]	SCHROEDER BW， VERHAEGHE C， PARK SW， et al. AGR2 is induced in asthma and promotes allergen-induced mucin overproduction [J]. Am J Respir Cell Mol Biol， 2012， 47(2):178-185.
[21]	NAKANISHI A， MORITA S， IWASHITA H， et al. Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma [J]. Proc Nat Acad Sci， 2001， 98: 5175–5180.
[22]	ROBICHAUD A， TUCK SA， KARGMAN S， et al. Gob-5 is not essential for mucus overproduction in preclinical murine models of allergic asthma [J]. Am J Respir Cell Mol Biol， 2005， 33(3): 303-314.