罗格列酮对哮喘小鼠肺组织GABAARα、MUC5AC表达的影响
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摘要
目的通过观察罗格列酮干预前后哮喘小鼠肺组织中GABAARα、MUC5AC表达水平及改变,初步探讨罗格列酮、GABAARα、MUC5AC三者之间的关系,为哮喘的早期干预治疗提供理论依据。方法取100只6～8周雌性BABL/C小鼠,随机分为5组,分别为对照组、哮喘模型组、地塞米松组、罗格列酮组、地塞米松加罗格列酮组,每组20只。最后一次激发后取小鼠血液及肺组织进行相关检测。结果肺组织苏木精-伊红(HE)染色,罗格列酮、地塞米松组小鼠肺组织炎性细胞浸润程度较哮喘模型组明显减轻。罗格列酮组、地塞米松组血清中白细胞介素(IL)-4和嗜酸性粒细胞趋化因子-1(Eotaxin-1)水平明显低于哮喘模型组,且高于正常对照组(P<0.05);而罗格列酮组小鼠血清中IL-4和Eotaxin-1水平高于地塞米松组与地塞米松+罗格列酮组(P<0.05)。罗格列酮组、地塞米松组GABAARα、MUC5AC蛋白表达明显低于哮喘模型组,且高于正常对照组(P<0.05);罗格列酮组GABAARα、MUC5AC蛋白表达水平低于地塞米松组而高于地塞米松+罗格列酮组(P<0.05)。结论罗格列酮可能通过下调GABAARα、MUC5AC蛋白的表达,降低哮喘小鼠血清中IL-4和Eotaxin-1水平,减轻气道黏液过度分泌,缓解哮喘急性发作时的严重程度。
Objective To preliminarily invetigate the relation among rosiglitazone,GABAARα and MUC5AC by observing the expression level change of lung tissue GABAARαand MUC5AC in asthmatic mice before and after the intervention in order to provide a theoretical basis for the early intervention treatment of asthma.Methods One hundred female BABL/C mice,6-8 weeks old,were randomly divided into 5 groups,control group,asthma model group,dexamethasone group,rosiglitazone group and dexamethasone plus rosiglitazone group,20 cases in each group.After last time excitation,the mouse blood and lung tissue were taken for conducting the related detection.Results The lung tissue HE staining showed that the lung tissue inflammatory cell infiltration degree in the rosiglitazone and dexamethasone groups was significantly reduced compared with the asthma model group;serum IL-4 and eotaxin-1 levels in the rosiglitazone group and dexamethasone group were significantly lower than those in the asthma model group and higher than those in the control group(P<0.05);the expression levels of GABAARαand MUC5AC protein in the rosiglitazone group were lower than those in the dexamethasone group,and higher than those in the dexamethasone plus rosiglitazone group(P<0.05).Conclusion Rosiglitazone may decrease serum IL-4 and Eotaxin-1 levels in asthmatic mice,as well as reduce the excessive secretion of airway mucus and relieve the severity of acute asthma attacks by downregulating the expression of GABAARαand MUC5AC protein.
Objective To preliminarily invetigate the relation among rosiglitazone,GABAARα and MUC5AC by observing the expression level change of lung tissue GABAARαand MUC5AC in asthmatic mice before and after the intervention in order to provide a theoretical basis for the early intervention treatment of asthma.Methods One hundred female BABL/C mice,6-8 weeks old,were randomly divided into 5 groups,control group,asthma model group,dexamethasone group,rosiglitazone group and dexamethasone plus rosiglitazone group,20 cases in each group.After last time excitation,the mouse blood and lung tissue were taken for conducting the related detection.Results The lung tissue HE staining showed that the lung tissue inflammatory cell infiltration degree in the rosiglitazone and dexamethasone groups was significantly reduced compared with the asthma model group;serum IL-4 and eotaxin-1 levels in the rosiglitazone group and dexamethasone group were significantly lower than those in the asthma model group and higher than those in the control group(P<0.05);the expression levels of GABAARαand MUC5AC protein in the rosiglitazone group were lower than those in the dexamethasone group,and higher than those in the dexamethasone plus rosiglitazone group(P<0.05).Conclusion Rosiglitazone may decrease serum IL-4 and Eotaxin-1 levels in asthmatic mice,as well as reduce the excessive secretion of airway mucus and relieve the severity of acute asthma attacks by downregulating the expression of GABAARαand MUC5AC protein.
引文
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[10]朱亚蕊,刘剑波.哮喘小鼠肺和下丘脑组织中γ-氨基丁酸受体ARα的表达[J].郑州大学学报(医学版),2012,47(2):218-223.
[11]ROSEN E D,SPIEGELMAN B M.PPARgamma:a nuclear regulator of metabolism,differentiation,and cell growth[J].J Biol Chem,2001,276(41):37731-37734.
[12]JIANG C,TING A T,SEED B.PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines[J].Nature,1998,391(6662):82-86.
[13]任旭斌,刘春涛,朱涛.荷包牡丹碱对哮喘小鼠肺组织α-SMA及气道重构的影响[J].四川大学学报(医学版),2010,41(4):626-629.
[14]徐传芹,郑玉龙,程伟.GABA和一叶秋碱对哮喘小鼠肺功能和黏液的影响[J].中国现代医学杂志,2009,19(23):3541-3545.
[15]徐传伟,郭山春,郑振文.γ-氨基丁酸治疗对哮喘患儿血浆P物质和降钙素基因相关肽含量的影响[J].中国当代儿科杂志,2013,15(2):102-104.
[2]HARRINGTON L E,HATTON R D,MANGAN P R,et al.Interleukin 17-producing CD4+effector T cells develop via a lineage distinct from the T helper type 1and 2lineages[J].Nat Immunol,2005,6(11):1123-1132.
[3]YABUMOTO Y,WATANABE M,ITO Y,et al.Expression of GABAergic system in pulmonary neuroendocrine cells and airway epithelial cells in GAD67-GFP knock-in mice[J].Med Mol Morphol,2008,41(1):20-27.
[4]FRITSCHY J M,MOHLER H.GABAA-receptor heterogeneity in the adult rat brain:differential regional and cellular distribution of seven major subunits[J].J Comp Neurol,1995,359(1):154-194.
[5]XIANG Y Y,WANG S H,LIU M Y,et al.A GABAergic system in airway epithelium is essential for mucus overproduction in asthma[J].Nat Med,2007,13(7):862-867.
[6]CURRAN D R,COHN L.Advances in mucous cell metaplasia:aplug for mucus as a therapeutic focus in chronic airway disease[J].Am J Respir Cell Mol Biol,2010,42(3):268-275.
[7]OH S H,PARK S M,LEE Y H,et al.Association of peroxisome proliferator-activated receptor-gamma gene polymorphisms with the development of asthma[J].Respir Med,2009,103(7):1020-1024.
[8]SERHAN C N,DEVCHAND P R.Novel anti inflammatory targets for asthma.A role for PPAR-gamma[J].Am J Respir Cell Mol Biol,2001,24:658-661.
[9]PATEL H J,BELVISI M G,BISHOP-BAILEY D,et al.Activation of peroxisome proliferator-activated receptors in human airway smooth muscle cells has a superior antiinflammatory profile to corticosteroids:relevance for chronic obstructive pulmonary disease therapy[J].J Immunol,2003,170(5):2663-2669.
[10]朱亚蕊,刘剑波.哮喘小鼠肺和下丘脑组织中γ-氨基丁酸受体ARα的表达[J].郑州大学学报(医学版),2012,47(2):218-223.
[11]ROSEN E D,SPIEGELMAN B M.PPARgamma:a nuclear regulator of metabolism,differentiation,and cell growth[J].J Biol Chem,2001,276(41):37731-37734.
[12]JIANG C,TING A T,SEED B.PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines[J].Nature,1998,391(6662):82-86.
[13]任旭斌,刘春涛,朱涛.荷包牡丹碱对哮喘小鼠肺组织α-SMA及气道重构的影响[J].四川大学学报(医学版),2010,41(4):626-629.
[14]徐传芹,郑玉龙,程伟.GABA和一叶秋碱对哮喘小鼠肺功能和黏液的影响[J].中国现代医学杂志,2009,19(23):3541-3545.
[15]徐传伟,郭山春,郑振文.γ-氨基丁酸治疗对哮喘患儿血浆P物质和降钙素基因相关肽含量的影响[J].中国当代儿科杂志,2013,15(2):102-104.