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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 被引量:7
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作者 陆远 赵霞 《南京中医药大学学报》 CAS CSCD 北大核心 2017年第2期207-211,共5页
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... 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、AGR2mRNA表达显著高于正常组(P<0.05),而mCLCA3mRNA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mCLCA3mRNA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、AGR2mRNA表达所致。 展开更多
关键词 固本防哮饮 哮喘缓解期 气道 杯状细胞增生 黏液高分泌
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Forkhead box protein A2 and T helper type 2-mediated pulmonary inflammation 被引量:3
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作者 Ling Sun Xiao-Ju Tang Feng-Ming Luo 《World Journal of Methodology》 2015年第4期223-229,共7页
The transcription factor forkhead box protein A2(FOXA2, also known as hepatocyte nuclear factor 3β or transcription factor 3β), has been found to play pivotal roles in multiple phases of mammalian life, from the ear... The transcription factor forkhead box protein A2(FOXA2, also known as hepatocyte nuclear factor 3β or transcription factor 3β), has been found to play pivotal roles in multiple phases of mammalian life, from the early development to the organofaction, and subsequently in homeostasis and metabolism in the adult. In the embryonic development period, FOXA2 is require d for the formation of the primitive node and notochord, and its absence results in embryonic lethality. Moreover, FOXA2 plays an important role not only in lung development, but also in T helper type 2(Th2)-mediated pulmonary inflammation and goblet cell hyperplasia. In this article, the role of FOXA2 in lung development and Th2-mediated pulmonary inflammation, as well as in goblet cell hyperplasia, is reviewed. FOXA2 deletion in airway epithelium results into Th2-mediated pulmonary inflammation and goblet cell hyperplasia in developing lung. Leukotriene pathway and signal transducers and activators of transcription 6 pathway may mediate this inflammation through recruitment and activation of denditric cell during lung developments. FOXA2 is a potential treatment target for lung diseases with Th2 inflammation and goblet cell hyperplasia, such as asthma and chronic obstructive pulmonary disease. 展开更多
关键词 FORKHEAD box protein A2 T HELPER TYPE 2 inflammation Pulmonary Development goblet cell hyperplasia
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FOXM1在呼吸道病毒感染致哮喘小鼠急性发作中的机制 被引量:2
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作者 步美玲 王金荣 +1 位作者 冯梅 孙立锋 《山东大学学报(医学版)》 CAS 北大核心 2023年第6期1-9,共9页
目的探讨呼吸道病毒感染诱发哮喘小鼠急性发作的致病机制。方法选取6~8周龄BALB/c雌性小鼠,随机分为正常对照组、哮喘组、Poly(I:C)组、RCM1+Poly(I:C)组和Poly(I:C)+RCM1组(后两组分别为提前和推后1 h给予RCM1),每组15只。利用屋尘螨(H... 目的探讨呼吸道病毒感染诱发哮喘小鼠急性发作的致病机制。方法选取6~8周龄BALB/c雌性小鼠,随机分为正常对照组、哮喘组、Poly(I:C)组、RCM1+Poly(I:C)组和Poly(I:C)+RCM1组(后两组分别为提前和推后1 h给予RCM1),每组15只。利用屋尘螨(HDM)构建哮喘小鼠模型,病毒类似物Poly(I:C)经鼻滴入模拟呼吸道病毒感染诱导小鼠哮喘急性发作,以罗伯特·科斯塔纪念药1(RCM1)选择性抑制叉头框M1(FOXM1)表达,留取小鼠肺组织和肺泡灌洗液(BALF)。测定气道狭窄指数评估哮喘小鼠模型,采用Rt-PCR、ELISA法检测小鼠肺组织和BALF的白介素4(IL-4)、白介素13(IL-13)、干扰素γ(IFN-γ)炎症因子的表达及肺组织FOXM1和黏蛋白5AC(MUC5AC)表达;流式细胞分选小鼠BALF中的细胞计数;采用苏木精-伊红染色法和免疫组化染色法观察各组小鼠肺组织和气道上皮细胞形态学改变及FOXM1和MUC5AC表达。结果哮喘组小鼠气道阻力较正常对照组增高,而Poly(I:C)组小鼠气道阻力较哮喘组增加,差异均有统计学意义(P<0.05);与正常对照组相比,哮喘组小鼠肺组织IL-4和IL-13的mRNA表达水平升高(P<0.05),IFN-γ的mRNA表达水平降低(P<0.05);Poly(I:C)组IL-4和IL-13的mRNA表达水平高于哮喘组、RCM1+Poly(I:C)组和Poly(I:C)+RCM1组(P<0.05),RCM1+Poly(I:C)组IFN-γ的mRNA表达水平高于Poly(I:C)+RCM1组(P<0.05);与正常对照组相比,哮喘组BALF中细胞总数、嗜酸性粒细胞、巨噬细胞及IL-4、IL-13表达水平升高(P<0.05),IFN-γ下降(P<0.05),Poly(I:C)组BALF中细胞总数、嗜酸性粒细胞、巨噬细胞及IL-4、IL-13、IFN-γ高于哮喘组、RCM1+Poly(I:C)组和Poly(I:C)+RCM1组(P<0.05),且RCM1+Poly(I:C)组IL-4、IL-13表达低于Poly(I:C)+RCM1组(P<0.05);哮喘组小鼠肺组织FOXM1和MUC5AC的mRNA表达水平高于对照组(P<0.05),Poly(I:C)组的表达水平则高于哮喘组、RCM1+Poly(I:C)组和Poly(I:C)+RCM1组(P<0.05),RCM1+Poly(I:C)组肺组织FOXM1 mRNA表达水平高于Poly(I:C)+RCM1组(P<0.05),而MUC5AC的表达水平低于Poly(I:C)+RCM1组(P<0.05);哮喘组小鼠肺组织支气管上皮增厚、排列紊乱并有炎性细胞浸润,FOXM1及MUC5AC蛋白表达较正常对照组增高,差异均有统计学意义(P<0.05),而Poly(I:C)组小鼠上述形态学表现及FOXM1、MUC5AC蛋白表达水平较哮喘组更为显著(P<0.05),RCM1+Poly(I:C)组和Poly(I:C)+RCM1组气道上皮细胞形态学及FOXM1、MUC5AC蛋白表达较Poly(I:C)组明显减轻(P<0.05)。结论呼吸道病毒感染通过激活FOXM1通路,诱发气道上皮杯状细胞过度增生及黏液分泌亢进,同时促进哮喘小鼠肺组织炎症因子分泌,加重肺组织炎症,增加气道阻力,导致哮喘发作。 展开更多
关键词 叉头框M1 病毒 哮喘 气道炎症 杯状细胞增生
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