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山东大学学报(医学版) ›› 2009, Vol. 47 ›› Issue (7): 16-20.

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nAChRα7在条件免疫反应治疗小鼠支气管哮喘中的作用机制

李化兵,韩秀珍,冯益真,王金荣,孙妍,孙立峰,伊迎春,李志鹏   

  1. 山东大学附属省立医院儿科, 济南 250021
  • 收稿日期:2008-04-21 发布日期:2009-07-16
  • 通讯作者: 韩秀珍(1943- ),博士生导师,教授,主要从事小儿心血管疾病研究。 Email:hanxz1119@yahoo.com.cn
  • 作者简介:李化兵(1979- ),硕士研究生,主要从事小儿心血管疾病研究。 Email: huabing1979@yahoo.com.cn
  • 基金资助:

    国家自然科学基金资助项目(30571739)。

Mechanism of nAChRα7 in treatment of bronchial asthma by a conditioned immune response

LI Huabing, HAN Xiuzhen, FENG Yizhen, WANG Jinrong, SUN Yan, SUN Lifeng, YI Yingchun, LI Zhipeng   

  1. Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China
  • Received:2008-04-21 Published:2009-07-16

摘要:

目的探讨nAChRα7在条件免疫反应治疗小鼠支气管哮喘中的作用机制。方法选4~6周龄的雌性BALB/C小鼠,用卵清蛋白(OVA)腹膜下注射致敏,OVA雾化吸入激发,建立支气管哮喘模型,健康对照组用PBS给予相同处理。将模型小鼠随机分为7组,每组15只。A组:CIR1组;B组:CIR2组;C组:常规治疗组;D组:常规治疗减量组;E组:单纯声音刺激组;F组:单纯糖精水刺激组;G组:空白对照组。以上7组每天给予哮喘激发1次,各治疗组在治疗间隔1?h后给予激发。健康对照组为H组,用PBS激发20周。治疗20周后,用流式细胞技术检测CD4+ T细胞胞膜上烟碱型乙酰胆碱受体alpha7(nAChRα7)与胞浆内IL4、IFNγ表达量,分析nAChRα7与IL4、IFNγ的相关性。结果①A、B、C组与G组比较,CD4+ T淋巴细胞表达nAChRα7、IL4明显降低(P<0.01),IFNγ增高(P<0.01);各因子在A、B及C组之间差异无统计学意义(P>0.05)。nAChRα7与IL4表达呈正相关(r=0.76,P<0.01),与IFNγ表达呈负相关(r=-0.69,P<0.01);②D、E、F、G组与H组相比,气道上皮增厚,管腔狭窄,管壁周围有大量炎症细胞浸润;A、B、C组经治疗后气道上皮及炎性浸润明显改善。结论以声音或糖精水为条件刺激,以普米克令舒加万托林雾化吸入为非条件刺激建立起的条件免疫反应,通过下调CD4+ T淋巴细胞上nAChRα7的表达,调节CD4+ T淋巴细胞的免疫功能,缓解小鼠支气管哮喘。

关键词: 哮喘;条件免疫反应;nAChRα7;CD4+ T淋巴细胞;小鼠

Abstract:

To explore the effect of nAChRα7 on bronchial asthma by conditioned immune response(CIR) and to explore its mechanism. MethodsAn experimental asthma model was reproduced in healthy BALB/C mice(female,46weeks old)by sensitization and stimulation with OVA. All mice were randomly divided into 7 groups: CIR1(A)group, CIR2(B) group, conventional therapy(C) group, low dose conventional therapy(D) group, noise(E) group, SAC(F) group, and blank control(G) group. All the groups were stimulated  with OVA at 1 hour after treatments once a day. In the healthy group(H) PBS was used for 20 weeks. After 20 weeks therapy, bronchoalveolar lavage fluid(BALF) was taken for counting EOS;  Spleens were taken to obtain CD4+ T lymphocytes and expression of neuronal acetylcholine receptor alpha 7 (nAChRα7), IL4 and IFNγ were determined by flow cytometry; The lungs were taken to observe the pathologic changes by the HE and MASSON staining. Results①  Expressions of nAChRα7 and IL4 were much lower, and IFNγ was much higher in groups A,B and C than those in group G(P<0.01), but no differences were found among groups A,B and C(P>0.05). nAChRα7 was positively correlated with Il4(r=0.76,P<0.01) and negatively correlated with  IFNγ(r=-0.69,P<0.01). ② Epithelium much thicker, lumens were much narrower, and inflammatory cells were much more in groups D, E, F and G than those in group H,and after treatment,groups A, B and C were improved.ConclusionBy downregulating nAChRα7 expression ih the CD4+ T lymphocytes, CIR can be used to treat asthma.

Key words: Asthma; Conditioned immune response; nAChRα7; CD4+ T lymphocytes; Mice

中图分类号: 

  • R725.6
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[2] 冯锐1,张海霞2,李红梅3. 脾切除术治疗特发性血小板减少性紫癜75例预后分析[J]. 山东大学学报(医学版), 2010, 48(11): 117-120.
[3] . 肺炎支原体下呼吸道感染的临床特征分析[J]. 山东大学学报(医学版), 2009, 47(9): 125-128.
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