平喘Ⅰ号对哮喘大鼠模型STAT6 Eotaxin蛋白含量及其mRNA表达和相关因子影响的实验研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:
     观察平喘Ⅰ号对哮喘大鼠模型信号转导子和转录激活子(STAT6)蛋白含量,嗜酸性细胞特异性趋化因子(Eotaxin)蛋白含量及其mRNA表达以及肺泡灌洗液(BALF)和血清中IL-4,IL-13含量及EOS数的影响,探讨平喘Ⅰ号对支气管哮喘的作用机理。
     方法:
     采用免疫组化法和原位杂交法检测哮喘大鼠模型STAT6,Eotaxin蛋白及其mRNA表达;酶联免疫吸附试验法(ELISA法)检测大鼠肺泡灌洗液及血清中IL-4,IL-13含量;Wright(瑞士)染色法测定BALF中WBC数,EOS数及分类。
     结果:
     1、哮喘大鼠模型组STAT6蛋白,Eotaxin蛋白及其mRNA表达明显高于正常对照组,经统计学处理有显著差异(P<0.01),中药低、中、高剂量组STAT6蛋白,Eotaxin蛋白含量低于模型组,其mRNA表达明显弱于模型组,经统计学处理,有显著差异(P<0.01),中药中、高剂量组与地塞米松组相近,无显著差异(P>0.05)。
     2、模型组支气管肺泡灌洗液及血清中IL-4、IL-13含量明显高于正常对照组,经统计学处理,有显著差异(P<0.01),中药低、中、高剂量组BALF及血清IL-4,IL-13含量明显低于模型组,有显著差异(P<0.01),中、高剂量组与地塞米松组相近,无显著差异(P>0.05)。
     3、哮喘模型组BALF中EOS绝对值及EOS%较正常对照组显著升高,经统计学处理有显著差异(P<0.01),中药低、中、高剂量组BALF中EOS绝对值及EOS%明显低于模型组,有显著差异(P<0.01),中、高剂量组与地塞米松组相近,无显著差异(P>0.05)。
     结论:
     平喘Ⅰ号通过降低哮喘大鼠模型STAT6蛋白、Eotaxin蛋白含量以及减弱STAT6 mRNA、Eotaxin mRNA在气道上皮细胞的表达,降低哮喘大鼠支气管肺泡灌洗液及血清中IL-4、IL-13含量,降低BALF中EOS数,来干预气道炎症,从而达到治疗支气管哮喘的目的。
Objective:
     Observe the influence of Chinese herbal medicine (PingChuan I ) to the asthma rat model STAT6 protein content, Eotaxin protein content and their mRNA and the contents IL-4、IL-13 and EOS numbers in the serum and BALF, inquiry into the function mechanism of PingChuan I to bronchus asthma.
     Method:
     Adopting immunohistochemical method and hybridization in situ method examination asthma rat model the expression of STAT6, Eotaxin protein and their mRNA; adopting enzyme linked immunosorbent assay(ELISA) to examine the contents IL-4、IL-13 in BALF and serum of rat, The Wright staining examine the WBC number、classification and EOS number in the BALF.
     Result:
     1.The asthma rat model group's STAT6 protein, Eotaxin protein and their mRNA's expression are obviously higher than the normal matched control, learned by covariance examination with obvious difference (P<0.01). Chinese herbal medicine low doses group, medium doses group and high doses group's the contents of STAT6 protein, Eotaxin protein is lower than model group, and their mRNA expression obviously weaker than model group, learned by covariance examination with obvious difference (P<0.01), but medium doses group, high doses group are close by dexamethasone group, no obvious difference (P>0.05).
     2. Model set's contents of IL-4,IL-13 in BALF and serum are obviously higher than normal matched control, learned by covariance examination with obvious difference(P<0.01). Chinese herbal medicine low doses group, medium doses group and high doses group's the contents of IL-4, IL-13 in BALF and serum are lower than that model group, but medium doses group, high doses group are close by dexamethasone group, no obvious difference (P>0.05)
     3. Asthma model group's #EOS and EOS% in BALF are obviously higher than normal matched control group, learned by covariance examination with obvious difference(P<0.01). Chinese herbal medicine low doses group, medium doses group and high doses group's #EOS and EOS% in BALF are obviously lower than model group's, learned by covariance examination with obvious difference(P<0.01), but medium doses group, high doses group are close by dexamethasone group, no obvious difference (P>0.05). Conclusion: The Chinese herbal medicine (PingChuan I ) may lower the contents of STAT6 protein and Eotaxin protein, and die down the expression of STAT6 mRNAs, Eotaxin mRNA in these asthma rats's airway epithelial cells, lower the contents of IL-4, IL-13 in the asthma rat's BALF and serum, lower the number of EOS in the BALF, tamper airway's inflammation, achieve the treatment purpose for the bronchus asthma.
引文
[1]甘慧娟,黄海,仲景治疗支气管哮喘方论,中医药导报,2006,(12)11:23-24.
    [2]董三艳,雷敏,中医药治疗支气管哮喘的优势评析,四川中医,2006,(24)12:21-23.
    [3]洪广祥,哮病治疗之我见[J],中医杂志,1988,26(3),7.
    [4]史锁芳,哮喘“夙根”探讨[J],中医药学报,1994,22(3):6.
    [5]邵长荣,喘有夙根—治喘务求其本[J],中国中西医结合杂志,1997,17(4):198.
    [6]尹良胜,吴银根教授中医药治疗哮喘经验,上海中医药大学学报,2006,(20)4:62-63.
    [7]马作峰等,邱幸凡论治支气管哮喘的思路方法,辽宁中医杂志2006,(33)12:1539.
    [8]符思,许卫华,王微,哮喘中医辨证论治研究进展,中国现代医药杂志,2006,(8)12:135-137.
    [9]张洪春,全国中医内科学会肺系病学术会议述要[J],中国医药学报,1992,(4):5.
    [10]孙继铭,从风论治支气管哮喘90例分析[J],实用中医内科杂志,2003,17(5):414.
    [11]王骏或,叶伟成,论温阳化瘀治哮喘[J],上海中医药杂志1994,(9):17.
    [12]杨华翠,许尤佳,中西医结合治疗小儿哮喘的远期疗效观察[J],湖北中医杂志,2000,22(8):17-18.
    [13]周仲瑛,哮喘杂谈[J],江苏中医2000,21(18):15.
    [14]张永涛,支气管哮喘的微观辨证学研究[J],江苏中医,1999,20(7):15.
    [15]张伟,邵雨萌,再论哮喘从瘀论治[J],湖南中医学院学报,2004,24(3):24.
    [16]武振东等,血府逐瘀汤为主治疗支气管哮喘61例观察[J],河南中医,2000,20(6):43.
    [17]李琳,22例支气管哮喘患者的血液流变学观察,中西医结合杂志,1989,(7):404.
    [18]朱鹏,复元活血汤治疗哮喘12例疗效观察,江西中医药1992,23(5):289.
    [19]于化鹏,过敏性哮喘中血小板功能变化及川芎嗪对哮喘防治作用的研究,中西医结合杂志,1991,11(5):291.
    [20]钱丽萍,补肾法治疗支气管哮喘的研究概况[J],时珍国医国药2005,16,(3):268.
    [21]张智娟,支气管哮喘从肾论治的中医药研究进展,甘肃中医学院学报,2006,23(6):39-42.
    [22]周兆山,王燕青,哮喘缓解期从肾虚体质辨证[J],中医研究2005,18(9):22-24.
    [23]欧广生,仙露哮喘康胶囊治疗支气管哮喘50例临床观察[J],湖南中医杂志,1996, 12(3):12.
    [24]柯新桥,补肾防喘述要[J],湖北中医杂志,1997,19(6):3-5.
    [25]史锁芳,李石青治疗支气管哮喘持续发作的经验[J],江苏中医,1995,16(8):35.
    [26]张洁承,支气管哮喘[J],山东中医杂志,1994,13(1):286.
    [27]包培蓉,吕同杰哮证治疗经验[J],中国中医急症,1995,4(5):29.
    [28]戴克敏,姜春华治疗哮喘的经验[J],安徽中医学院学报,1990,9(3):17.
    [29]陈济德,苏子降气汤和旋覆代赭汤加减治疗哮喘65例[J],山东中医杂志,1994,13(1):298.
    [30]宋勉,王亚梅,肺肠同治在治疗支气管哮喘急性发作期的应用[J],光明中医,2005,20(1):5.
    [31]崔乃会,武翠凤,通腑泻肺法治疗顽固性哮喘53例[J],陕西中医,1999,20(10):466.
    [32]苏慧萍,通腑法治疗哮喘发作期的临床应用[J],北京中医药大学学报,1995,18(5):64.
    [33]史锁芳,曹世宏治疗支气管哮喘经验[J],江西中医药,1998,29(6):76.
    [34]李家裕,审证求因治哮喘—张鸿祥经验谈,上海中医药杂志,1996,(4):24.
    [35]李向东,蒋雅萍,蔡寅寿,健脾益肺口服液治疗小儿哮喘缓解期50例[J],陕西中医,2003,24(6):499.
    [36]张锦珠,王建明,补肺益肾汤治疗支气管哮喘32例[J],陕西中医,1995,16(10):439-440.
    [37]刘士敬,泻肾法在治疗支气管哮喘中的应用,云南中医学院学报,1997,20(2):29-31.
    [38]符晓,王大海,龚兴宏等,补肾温肺胶囊治疗支气管哮喘缓解期患者的疗效观察[J],中国中西医结合杂志,2001,21(9):699-700.
    [39]宋涌文,温肾健脾祛痰法控制支气管哮喘复发30例-附核酪注射液治疗对照22例,浙江中医杂志,1998,(1):28-29.
    [40]吴银根等,健脾温肾膏方治疗哮喘120例远期疗效分析[J],浙江中医杂志,2000,(4):144.
    [41]武维萍,贺福田,肝与咳、喘、哮,北京中医学院学报,1990,13(2):11.
    [42]武维萍,田秀英,王琦等,调肝理肺法治疗哮喘174例临床观察,北京中医学院学报1990,13(4):19
    [43]王德玉,柴可群,咳喘从肝论治,浙江中医学院学报,1993,17(4):10.
    [44]康景华,纪晓泉,辨证治疗支气管哮喘58例临床观察[J],天津中医,1994,11(6):27.
    [45]武维萍,支气管哮喘临床研究评述[J],中医函授通讯 1999,918(1):22.
    [46]王有奎,以理肺补肾法治疗208例支气管哮喘[J],中医药研究,1990,6(6):48.
    [47]夏永良,王彩霞,李德新,哮喘缓解期从脾论治机理的研究[J],中医药学刊,2003,2(7):1194.
    [48]刘继堂,支气管哮喘缓解期的治疗[J],河南中医,1996,16(1):15.
    [49]柯新桥,补肾防喘述要,湖北中医杂志,1997,19(6):3.
    [50]李智,哮病辨证体系探讨[J],中国中医基础医学杂志,2002,8(8):785-787.
    [51]周仲瑛,哮喘杂谈[J],江苏中医,2000,21(8):1.
    [52]李明华,哮喘病学[M],北京人民卫生出版社,1998,44-45.
    [53]崔新乐,朱之珏,一氧化氮与哮喘[J],国外医学·呼吸系统分册,1996,(16):1012.
    [54]蔡宛如等,芍药甘草汤平喘和抗过敏的实验研究[J],中国中西医结合急救杂志,2000,11(6):341—342.
    [55]王力宁等,六味地黄丸协同必可酮对致敏豚鼠气道反应性和血嗜酸细胞的影响[J],广西中医药,2001,12(6):51-53.
    [56]张建勇,火把花根片对哮喘豚鼠气道炎症的作用[J],贵州医药,2001,11(10):890-892.
    [57]方向明等,平喘宁对哮喘豚鼠一氧化氮,肿瘤坏死因子影响的实验研究[J],中国中医基础医学杂志,2002,2(3):42-44.
    [58]邢向晖等,平喘方对哮喘大鼠平喘作用的实验研究[J],中国中医药信息杂志,2002,9(12):17.
    [59]肖丽玲等,定喘汤对哮喘大鼠NO、ET、IL—5的影响[J],中国实验方剂学杂志,2005,11(3):58.
    [60]王志英等,平喘口服液治疗支气管哮喘的临床和实验研究[J],中国中西医结合杂志,2000,20(10):739.
    [61]王宏长等,咳喘落对哮喘患者酸性粒细胞阳离子蛋白的影响[J],上海中医药杂志,2003,(3):16.
    [62]王宏长等,中药咳喘落对实验性哮喘豚鼠ECP和SICAM-1的影响[J],广东中医杂志,2000,21(3):188.
    [63]金美玲等,CPGDNA治疗变应性哮喘的研究进展[J],实用医学杂志,1999,7,(15):585.
    [64]黄慧,支气管哮喘中Th1/Th2,模型漂移的研究进展,国外医学,内科学分册,2002,29(6):247.
    [65]Marphy E,Shibnya K,Hosken N,etal, Reversibility of Thelper 1 and 2 populations is lost after long-term stimulation[J].J Exp Med 1996,183(3):901.
    [66]王长征等,雷公藤甲素对哮喘动物模型气道反应的观察[J],中华医学杂志,1996,76(1):68.
    [67]赵晓东等,黄芪对哮喘患儿INF-r,IL-4及IgE亚类体外产生的影响[J],中国实用儿科杂志,1997,12(6):345.
    [68]张在期等,小青龙汤对哮喘小鼠肺组织Th1/Th2作用的实验研究,中国中西医结合急救杂志,2004,11(6):368.
    [69]薛汉荣等,益气温阳护卫汤对哮喘豚鼠BALF中Th1,Th2细胞因子产生及调节的作用,中国医药学报,2002,17(3):152.
    [70]壮健等,消喘膏贴敷对哮喘豚鼠Th1,Th2类细胞因子的影响,四川中医,2003,21(6):13.
    [71]薛汉荣等,益气温阳护卫汤对缓解期哮喘患者气道反应性的影响及作用机理研究[J],中国医学学报,2004,19(8):477.
    [72]李彤,平哮合剂对哮喘气道高反应性的影响[J],山西中医,2001,17(3):44.
    [73]王长征等,致敏豚鼠的气道高反应机理及药物干预作用[J],中国病理生理杂志,1997,13(1):8.
    [74]Fish JE,Peters SP.Airway remodeling and persistent airway obstruction in asthma [J]. J Allergy clin Immunol 1999,104:509.
    [75]Hoshino M,Nakamura Y, Hanid QA.Gene expression of vascular endoehelial growth factor and its receptors and angiogenesis in bronchial asthme[J].J Allergy clin Immunol 2001,107:1034-8.
    [76]吴银根等,基质金属蛋白酶及其抑制剂在哮喘气道重塑中的作用及止咳胶囊的干预[J],中西医结合学报,2004,2(6):435.
    [77]汪珊等,中药地龙药理与哮喘气道重建相关性研究[J],广东药学院学报,2004,20(1):60.
    [78]Hogan SP, Koskiner A,Matthaei KI,etal.Interleukin-5-producing CD4~+ T cells paly a pivotal role in aeroallergen-induced eosinophilia,bronchial hyperreactivity and lung damage in mice Am[J].Respir Crit Care Med I998,157(1):210-218.
    [79]张全爱等,哮喘模型豚鼠变态反应机制的实验研究[J],甘肃中医学院学报,2003,20(4):16-17.
    [80]魏庆宇等,加味玉屏风散对哮喘大鼠支气管上皮ICAM-1的表达及BALF中Ⅱ-5含量的影响[J],中国实验方剂学杂志,2001,7(5):40-42.
    [81]郭素华等,加味肾气丸对Th1,Th2细胞凋亡及细胞因子表达影响的研究[J],贵阳中医学院学报,2004,26(1):48-50.
    [82]王宏长等,中药咳喘落对实验性哮喘豚鼠ECP和SICAM-1的影响[J],广东医学,2000,21(3):188-190.
    [83]赵育芳等,太子健Ⅱ对哮喘豚鼠白细胞介素5、P-选择素的影响[J],山西医药杂志,2004,33(7):565-567.
    [84]Hamann KJ,Vieria JE,Halayko AJ etal Fas. cross-linking induces apoptosisi inhuman airway Smooth muscle cell Am[J].physiol lung cell Mol physiol 2000, 278 (3):L618-628.
    [85]刘贵颖等,咳喘方对哮喘豚鼠肺组织嗜酸细胞凋亡的影响[J],天津中医药,2004,21(4):315-317.
    [86]伍参荣等,治喘贴对实验豚鼠嗜酸粒细胞凋亡和对白细胞介素-5的影响[J],中华微生物学和免疫学杂志,2004,24(7):549.
    [87]方向明等,平喘合剂对哮喘豚鼠T淋巴细胞凋亡的影响[J],中国中医基础医学杂志,2003,9(3):184-186.
    [88]林科雄,雷公藤对哮喘豚鼠IL-5、GM-CSF基因转录的影响与作用机制[J],中国免疫学杂志,2000,(9):325-327.
    [89]李志奎等,雷公藤甲素对哮喘豚鼠嗜酸性粒细胞凋亡及Fas、Bcl-2、MRNA表达的影响[J],中国新药与临床杂志,2002,5(5):261-262.
    [90]王宏长等,中药哮喘落对哮喘大鼠肺组织白细胞介素-4、Il-5 MRNA影响及相关性研究,广东医学,2000,21(2):107.
    [91]范欣生等,复方辛夷平喘液对哮喘豚鼠肺内ICA及淋巴细胞fas表达的影响,中华结核和呼吸杂志,2002,25(5):280.
    [92]陈文彬,争取获得慢性阻塞性肺病及哮喘更理想的诊断与治疗,实用医院临床杂志,2007,4(1)1-2
    [93]SchindlerC,DarnellJEJr.Transcriptional responses to polypeptide ligands:the JAKSTAT pathway[J]. Annu Rev Biochem,1995,64:621-51.
    [94]叶乐平等,信号转导子和转录激活子6与支气管哮喘[J],国外医学儿科学分册,2003,30,(5):234-236.
    [95]周玲等,STAT蛋白与肺部疾病,国际呼吸杂志,2006,26,(12):951-953.
    [96]Yumiko K,HyunJL,James AJ,etal.Aconditionally active form of STAT6 canmimic certain effects of IL-4.J Immunol, 1998,161:1074-1077.
    [97]盛青等,STAT6与支气管哮喘,国外医学呼吸系统分册,2004,24(1):12-14.
    [98]HuangH,PaulWE.Protein tyrosinephosphatase activityis required for IL-4induction of IL-4 reeept orα-chain[J].J Immunol,2000, 164(3): 1211-5.
    [99]DickensheetsHL,Venkataraman C,SchindlerU,etal.Interferons inhibit activation of STAT6 by interleukin4 in humanm monocytes by inducingSOCS-lgene expre-ssion [J].ProcNatl AcadSci USA, 1999,96(19): 10800-5.
    [100]ChoSS,Bacon CM,Sudarshan C,etal. Activation of STAT4 byIL-12 and IFN-α [J]. JImmunol, 1996,157(11):4781-9.
    [101]MurphyKM,OuyangW, FarrarJD,etal.Signaling and transcription in The lper development.AnnuRevImmunol,2000,18(1):451-494.
    [102]Alessandra B,Pernisand Paul B,Rothman.JAK-STAT signaling in asthma.J Clin Invest, 2002,109(10),1279-1283.
    [103]FinottoS,DeSanctisGT, LehrHA,etal.Treatment of allergi cairway inflammation and hyperresponsiveness by antisense-induced local block ade of GATA-3 expression. J Exp Med,2001,193(11):1247-1260.
    [104]TomkinsonA,KanehiroA,RabinovithchN,etal.The failure of STAT6-deficient Mice to develop airwaye osinophilia and airway hyperresponsivenessis over come by interleukin-5. Am J Respir Crit Care Med,1999,160:1283-1291.
    [105]AkimotoT,NumataF,TamuraM,etal.Abrogation of bronchial Eosinophilic inflammation and airway hyperreactivityin signal transducers and activators of transcription (STAT)6-deficientmice.J Exp Med,1998,187:1537-1542.
    [106] MathewA,MacleanJA,DehannE,etal.signal transducer and activator of transcription6 control schemokine production and Thelpercell type2 cell traffickingin allergic pulmonary inflammation.JExpMed,2001,193 : 1087-1096.
    [107] WangLH,YangXY, KirkenRA.Targeteddisruption of stat6 DNA binding activity by an0bligonucleotidedecoy blocksIL-4 driven Th2cellresponse. Blood, 2000, 95:1249-1257.
    [108] KupermanD,SchofieldB,Wills-karpM,etal.SignalTransducer and activator of Transcription factor6(stat6)-deficient Miceare protected from antigen-induced airway hyperresponsiveners and mucusproduction.JExpMed, 1998, 187:939-948.
    [109] DuetschG, IllingT, LoesgenS,etal.STAT6 as an asthma candidate gene: polymorphism-screening association and haplotype analysis in acaucusiansib-pair study. HumMolGenet,2002,11:613-621.
    [110] KamogawaY, LeeHJ,JohnstonJA,etal.Cuttingedge:aconditionally active form of STAT6 canmimic certain effects of IL-4[J].JImmunol,1998,161(3):1074-7.
    [111] QuelleFW, ShimodaK,ThierfelderW, etal.Cloning of murine Stat6 and human Stat6,Stat proteins that are tyrosinephosphorylated in responses to IL-4 and IL-3 but are not required form itogenesis[J].MolCellBiol, 1995,15(6):3336-43.
    [112] KaplanMH,GrusbyMJ.Regulation of The lper cell differentiation by STAT molecules [J]. JLeukoeBiol, 1998, 64(1):2-5.
    [113] MullingsRE,WilsonSJ,PuddicombeSM,etal.Signal transducer and activator of transcription6(STAT-6) expression and function in asthma ticbronchialepithelium [J]. JAllergyClinImmunol,2001,108(5):832-8.
    [114] AkimotoT, NumataF, TamuraM,etal.Abrogation of bronchial eosinophi-lic inflammation and airway hyperreactivity in signal transducers and activators of transcription(STAT)6-deficientmice[J].JExpMed, 1998, 187(6): 1537-42.
    [115] MathewA,MacLeanJA,DeHaanE,etal.Signal transducer and activator of transcript-tion6 controls chemokine production and The lpercell type2 cell trafficking in allergicpulmonaryinflammation[J]. JExpMed,2001,193(9):1087-96.
    [116] TomkinsonA,DuezC,LahnM,etal.Adoptive transfer of Tcelis induces airway hype-rresponsiveness independently of airwaye osinophilia but in signal transducer and activator of transcription6-dependentmanner[J]. J Allergy Clin Immunol,2002, 109(5):810-6.
    [117]PernisAB,RothmanPB.JAK-STAT signaling in asthma[J]. J Clin Invest, 2002, 109 (10):1279-83.
    [118]AkimotoT, NumataF, TamuraM,etal.Abrogation of bronchial Eosinophilic inflammation and airway hyperreactivity in signal transducers and activators of transcription(STAT)b-deficientmice.J Exp Med, 1998,187:1537-1542.
    [119]KupermanD,SchofieldB,Wills-karpM,etal.Signal Transducer and activator of Transcription factor6(stat6)-deficient Mice are protected from antigen-induced airway hyperresponsiveners and mucusproduction.J Exp Med, 1998,187:939-948.
    [120]MatsukuraS,StellatoC,PlittJR,etal.Activation of eotaxin gene transcription byNF-κB and STAT6 in Human airway epithelialcells. JImmunol, 1999,163:6876-6883.
    [121]MullingsRE,WilsonSJ,PuddicombeSM,etal.Signal transducer and activator of transcription6(STAT6) expression and function in asthmatic bronchial epithelium. J Allergy Clin Immunity,2001,108:832-837.
    [122]AkihoH,BlennerhassettP, DengY, etal.Role of IL-4,IL-13and STAT6 in inflammation-induced hypercontractility of murine smooth muscle cells. Am J Physiol Gastrointest Liver Physiol2002, 282:G226-232.
    [123]HeinH,SchlterC,KulkeR,etal.Genomic organization, sequence,and transcriptional regulation Of the human eotaxin gene.Biochem Biophys Res Commu, 1997;237: 537—542.
    [124]Crump M P, RajarathnamK,KimKS,etal.Solution structure of eotaxin,achemokine that Selectively recruits eosinophils in allergic inflammation. J Biol Chem, 1998;273: 22471-22479.
    [125]PonathPD,QinSX,RinglerDJ,etal.Cloning of the human eosinophii chemoattractant, eotaxin.J Clin Invest, 1996;97:6042612
    [126]金蕊,嗜酸粒细胞与支气管哮喘的治疗,国外医学儿科学分册,2004,31(4)
    [127]李静,趋化因子EOTAXIN及其受体与支气管哮喘,国际儿科学杂志,2006,33(3):406-408.
    [128]Bandeira2MeloC,HerbstA,WellerPF.Eotaxins.Contributing to the diversity of eosinophil recruitment and activation[J] . AmJ Respir Cell MolBiol, 2001,2 4(6): 653-657.
    [129] KomiyaA,NagaseH,YamadaH,etal.Concerted expression of eotaxin-1,eotaxin-2 and eotaxino3 in human bronchial epithelial cells[J].Celllmmunol, 2003,225(2): 91-100.
    [130] KumarRK,ThomasPS,SeetooDQ,etal.Eotaxin expression by epithelial cells and plasma cells in chronic asthma[J].Lablnvest,2002,82(4):495-504.
    [131] LiD,WangD,Griffiths2JohnsonDA,etal.Eotaxin protein and gene expression in guinea-pig lungs: constitutive expression and up regulate after allergen challenge [J]. EurRespirJ, 1997,10(9): 194621954.
    [132] HochestetterR.Dobos G, kimmigD.etal The CC chemokine receptor 3 eeR3 is functionally expressed on eosinoplils but not on neutrphils (J).Eur J Immanuel 2000,30(10) 2759-2764.
    [133] Zimmermann N Coukright JJ. Rothenberg ME ,CC Chemokine receptors-3 undergoes prolonged ligand-induced internalization (J) J Bid chem. 1999, 274: 12611-12618.
    [134] Kempen GT .Staffords. Adachi T, Eo taxin induces degrannlation and chemotaxs of eosinophils through the activation of EK K2 and p38 mitogen activated protein kinases (J).Blood,2000,95,1911-1917.
    [135] Ponath po .Qin SX .Ringler DJ ,etal . Cloning of the human eosinophil chemo attractant, eotaxin (j) J Clin invest , 1996,97:604-612.
    [136] Mould AW. Matthaei KI, Young IG, etal. Relationship between interleukins and eotaxin in regulating blood and tissue eosinophilia in mice (J) J Clin Invest,1997, 99:1064-1071.
    [137] 李凝,许以平,CCL趋化因子和支气管哮喘(J),国外医学,呼吸系统分册,2001,21(3):118-121.
    [138] Hanazawa T .Antuni JD .Kharitonov .SA ,etal .Intranasal administration of eotaxin increase nasal eosinophils and nitricoxide in patients with allergic rhinitis (J) J Allergy Clin Immunol ,2000,56-64.
    [139] G Arcia-Zepeda F.A.Rothenberg ME.Weremowicz S etal Genomic organization, complete sequence and chromosomal location of the gene for man eotaxin (SCYALL), an eosnophil-specific CC chemoline(J). Gememic, 1997, 41(3) 471-476.
    [140] 高贵民,嗜酸性粒细胞活化趋化因子与支气管哮喘的研究进展,国际免疫学杂志2006,29(2):93-96.
    [141] ImGJ,HwangCS,JungHH.Quantitative expression levels of regulated on activation,normal Tcell Expressed and secreted and eotaxin transcriptsin to luenediiso-cyanate 2 induced allergicrats.ActaOtolaryngol,2005, 125(4):370-377.
    [142] JusticeJP, BorchersMT, CrosbyJR,etal.Ablation of eosinophils lead sareduction of allergen induced pulmonary pathology[J]. Am J Physiol Lung Cell MolPhysiol, 2003, 245(1):L169-178.
    [143] KimJ,MerryAC,NemzekJA,etal.Eotaxin represents the principal eosinophil chemo attract antinanovel murine asthma mode induced by house dust containing cock roacha llergens.J Immunol2001,167:2805-2815.
    [144] ZimmermannN,ConkrightJJ,RothenbergME.CC chemokin receptor 23 undergoes prolong edligand 2 induced internalization.JBioChem, 1999,274: 12611-12618.
    [145] KampenGT, StaffordS,AdachiT.Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen2 activated protein kinases.Blood,2000,95:19112.
    [146] YingS,MengQ,ZeibecoglouK,etal.Eosinophil hemotactic hemokines eotaxin, eotaxin-2, RANTES,monocyte hemottractant rotein(MCP)23,and CP24,and CC hemokines receptor 3 expression in bronchial biopsiesfromatopic and nonatopic asthmatics [J]. JImmunol,1999,163(11):63-129.
    [147] NakamuraH,WeissST, IsraelE,etal.Eotaxin and impaired lung function in asthma [J].Am J Respir Crit Care Med, 1999,160(6):1952-6.
    [148] YamadaH,YamaguchiM,YamamotoK,etal.Eotaxin in induced sputum of asthmatics: relationship with eosinophils and eosinophil cationic protein in sputum [J].Allergy,2000,55(4):392-7.
    [149] BrownJR,KleimbergJ, MariniM,etal.Kinetics of eotaxin expression and its relationship to eosinophil accumulation and activation in bronchial biopsies and bronchial veolarlavage of asthmatic patients after allergen inhalation [J]. ClinExplmmunol, 1998,114(2): 137-146.
    [150] 叶飒,CC趋化因子受体3及其拮抗剂与支气管哮喘,国外医学呼吸系统,2005,1(25):4.
    [151] Genzalo JA,etal.JExp Med, 1998,188:157-167.
    [152] Ying S,etal.J Immunol,1999, 163:6321-6329.
    [153] Nakamura H, etal.Am J Respir Crit Care Med ,1999, 160 1952-1956.
    [154] Kitayama J, etal. J Clin Invest ,1998, 101:2017-2024.
    [155] LiD,WangD,GriffithsJ ohnsonDA,etal.Eotaxin protein and gene expression in guinea-pig lungs:Constitutive expression and up regulation after allergen challenge. EurRespirJ, 1997;10:1946-1954.
    [156] MattoliS,StaceyMA,SunG, etal.Eotaxin expression and eosinophilic inflammation in asthma. BiochemBiophysResCommun, 1997;236:299-301.
    [157] TahaRA,MinshallEM,MiottoD,etal.Eotaxin and monocyte chemotactic protein24 mRNA expressin In small airways of asthmatic and non asthmatic individuals. Jallergy Clinlmmunol, 1999; 103:476-483.
    158 BrownJR,KleimbergJ,MariniM,etal.Kinetics of eotaxin expression and its relationship to eosinophil accumulation and activation in bronchial biopsies and bronchial veolarlavage(BAL)of Asthmatic patients after allergen inhalation. ClinExp Immunol, 1998;114:137-146.
    [159] UguceioniM,MackayCR,OchensbergerB,etal.High expression of the chemokine receptor CCR3 in human blood basophils.JClinlnvest,1997;100:1137—1143
    [160] SallustoF,Mackay CR,LanzavecchiaA.Selective expression of the eotaxin receptor CCR3 by human T helper2 cells.Science,1997;277:2005-2007.
    [161] GerberBO,ZanniMP, UguccioniM,etai.Functional expression of the eotaxin receptor CCR3 in Tlymphocytesco localizing with eosinophils. CurrBiol, 1997;7: 836-843.
    [162] GhaffarO,HamidQ,RenziPM,etal.Constitutive and cytokine stimulated expression of eotaxin by human airway smooth muscle cells.Am J Respir Crit Care Med, 1999; 159:1933-1946.
    [163] HanSJ,KimJH,NohYJ,etal.Interleukin(IL)-5 down regulates tumornecros is factor(TNF)induced eotaxin messengerRNA(mRNA) expression in eosinophiis.Am J Respir Cell MolBiol, 1999;21:303-310.
    [164] ZhuZ,HomerRJ,WangZ,etal.Pulmonary expression of interleukin-13 causes Inflam-mation,mucushyper secretion,subepi the lial fibrosis, physiologicab normalities, and eotaxin production. JClinInvest, 1999;103:779-788.
    [165] LiL,XiaY, NguyenA,etal.Effects of Th2 cytokines on chemokine expression in the lung:IL-13 potently induces eotaxin expression by airway epithelial cells. JImmu-nol, 1999; 162:2477-2487.
    [166] CampbellE,KunkelSL,StrieterRM,etal.Differential roles of IL-18 in allergic airway disease:induction of eotaxin by resident cell Population sex acerbates eosinophilaaccumulation.JImmunol,2000; 164:1096-1102.
    [167] KumagaiN,FukudaK,IshimuraY, etal.Synergistic induction of eotaxin expression inhuman keratocytes byTNF-alpha and IL-4 or ILl3 .Invest Ophthalmol VisSci, 2000; 41:1448-1453.
    [168] erradaN,HamanoN,NomuraT,etal.Interleukin-13 and tumournecrosis factor2 alphasynergistically induceeotaxinproduction in human nasal fibroblasts. ClinExpAllergy, 2000;30:348-355
    [169] LillyCM,NakamuraH,KesselmanH,etal.Expression of eotaxin by human lung epithelial cells.JClinlnvest, 1997;99:1767-1773.
    [170] Garcia Zepeda EA,Rothen berg ME,Weremowicz S,et al.Genomic organization, complete sequence, and chromosom allocation of the gene for human eotaxin (SCYA11), an eosinophii 2 specific CC chemokine. Genomics, 1997;41(3): 471-476.
    [171] HeinH,SchlerC,KulkeR,etal.Genomic organization, sequence analysis and transcriptional regulation of the human MCP24 chemokine gene (SCYA13) indermalfibroblasts: acomparisonto Other eosinophilic beta2 chemokines. Biochem BiophysRes Commun,1999;255:470-476.
    [172] Garcia-ZepedaEA,RothenbergME,OwnbeyRT, etal.NatMed, 1996,2:449-456.
    [173] Barnes PJ Cytokines as mediators of chronic asthma. Am J Respir Crit Care Med 1994 Nov;150(5Pt2):S42-9.
    [174]黄慧,支气管哮喘中Th1/Th2模型漂移的研究进展[J],国外医学内科学分册,2002,6,29(6):247.
    [175]TamuraK, ArakawaH, SuzukiM, etal.Noveldinucleotiderepeatpolymorphism in the first exonof the STAT-6 geneisas-sociated with allergic diseases [J].ClinExp Allergy, 2001, 31(10):1509~14.
    [176]MullingsRE,WilsonSJ,PuddicombeSM,etal.Signal transducer and activator of transcription 6(STAT-6)expression and function in asthma ticbronchial epithelium[J]. J Allergy Clin Immunol,2001,108(5):832-8.
    [177]McKenzieAN.Regulation of The lpertype2 cell immunity by interleukin-4and interleukin-13 [J].pharmacolther,2000,88(2): 143-151.
    [178]KraneveldAD,FolkertsG, VanOosterhout AJ,etal.Airway hyperresponsiveness:first eosinophils and the neuropeptides[J]. IntJ Immunol pharmacol, 1997, 19 (9-10):517~27.
    [179]Marsha Wills-karp,JackieLuyimbazi,XueyingXu,Inter-leukin-13:Central Mediator of Allergic Asthma[J]. Science, 1998,18:282,2258.
    [180]Taroshirakawa,KlausA.Deichmann,Kenjilzuhara,etal Atopy and asthma [J]. Immunol ogytoday,2000,21 (2):61.
    [181]YangM,HoganSP, HenryPJ,etal. Interleukin-13 mediates airways hyperreactivity through the IL-4receptor-alphachain and STAT-6independently of IL-5 and eotaxin [J].Am J Respir Cell MolBiol,2001,25(4):52230.
    [182]CoffmanRL,OharaJ,BondMW etal.J Immunol, 1996,146.
    [183]TapperRI,LevinsonDA,StrangerBZ,etal.IL-4 induces allergilike inflammatory DiseaseandaltersT cell development in trans-genicmice.Cell, 1990,62:457-467.
    [184]BurstenHJ,etal.Cell, 1991,62:457.
    [185]刘晓菊,邢祖林,白细胞介素-4和干扰素-γ对哮喘患者外IgE合成调控的研究[J],中华结核和呼吸杂志,1996,19(5):286~289.
    [186]WardlawAJ,Eosinohils in the1990s:newperspectives On the irroinhtalth and Disease [J], 1994,70(826):536~552.
    [187]周云桂,黄绍良,李树浓,etal,中国免疫学杂志,1997,13(6)382.
    [188]TakeshiF, YaxutsuguF, ToshiN,etal,Roleofinterlerkin-4 An Vascular cell adhesion molecule-linselective eosinophil migratio into the airways in allergic asthma. Am J Respir Cell Mol Biol, 199614:84~94.
    [189] Anderson GP, CoyleAJ.TH2 and"TH2-1ike"cells in allergy and asthma:pharmacol ofical perspectives.TrendsPharmacolSci, 1994,15(9):324-332.
    [190] MarshDG,Neely JD,BreazealeDR,etaI.Linkage analysis of IL4 and other Chromosom 5931.1Markers and total serumim-munoglobul in Econcertrations. Science. 1994,264(5162):1152-1156.
    [191] Borish L,Rosenwasser Lj,Update on cytokines,J Allergy Clin Immunol,1996,97 (3):719-733.
    [192] OkayamaY, Petit-FrereC,KasselO,etal,IgE-Dependent expression of mRNA for IL-4 and IL-5 in Human MastCells.JIm-munol. 1995,155(4):1796-1808.
    [193] SchleimerRPS,SterbinskySA,KaiserJ,etal. IL-4 induces adherence of humaneosino-phils and basophils but not neutrophil stoen-dothelium. Association with expression of VCAM-1. JIm-munol. 1992,148(4): 1086-1092.
    [194] Wills-KarpM,LuyimbaziJ,XuX,etal Interleukin-13: centralme-diator of allergic asthma[J].Science, 1998,282(5397):2258-2261.
    [195] BlackburnMR,LeeCG, YoungHW, etal Adenosine mediates IL-13-induced inflammation and remodeling in the lung and interactsinan IL-13-adenosineam-plification pathway[J]. JClinInvest,2003,112(4):332-344.
    [196] CohnL,TepperJS,BottomlyK.IL-4 independent induction of airway hyperresponsiveness by Th2,but not Thl,cells[J].JImmu-nol,1998,161(8): 3813-3816.
    [197] ZhuZ,HomerRJ,WangZ,etal Pulmonary expression of interleukin-13 causes inflammation,mucushy persecretion,subepithe lialfi-brosis, physiologicab normalities, and eotaxin production[J].JClinInvest, 1999,103(8):779-788.
    [198] ZhuZ,MaB,ZhengT, etal IL-13 induced chemokine responses in the lung:role of CCR2 in the pathogenesis of IL-13 induced inflammation and remodeling[J]. JImmunol, 2002,168(6):2953-2962.
    [199] MaB,ZhuZ,HomerRJ,etal TheC10/CCL6 chemokine and CCRI play critical roles in the pathogenesis of IL-13-induced inflammation and remodeling[J]. J Immunol, 2004, 172(3):1872-1881.
    [200]ChenQ,RabachL,NobleP, etal IL-11 receptor{alpha} in the pathogenesis of IL-13-induced inflammation and remodeling[J]. JImmunol,2005, 174(4): 2305-2313.
    [201]CohnL,EliasJA,ChuppGL.Asthma:mechanisms of disease persistence and progression [J]. AnnuRevImmunol,2004,22(8):789-815.
    [202]WalterDM,MclntireJJ,BerryG, etal Criticalrole for IL-13 in the development of allergen-induced airway hyperreactivity[J]. JImmunol, 2001,167(8):4668-4675.
    [203]TlibaO,DeshpandeD,ChenH,etal IL-13 enhances agonist-evokedcal cium signals and contractile responses in airway smooth muscle[J]. BrJPharmacol, 2003, 140 (7): 1159-1162.
    [204]DeshpandeDA,DoganS,WalsethTF,eta.lModulation of calcium signaling by interleukin-13 in human airway smooth muscle:role of CD38/cyclicade nosine diphosphateribose pathway[J].Am J Respir Cell Mol Biol,2004,31 (1):36-42.
    [205]EspinosaK,BosseY, StankovaJ,etal CysLT1 receptor up regulation by TGF-beta and IL-13 is associated with bronchial smooth muscle cell proliferationin response to LTD4 [J].JAllergyClinImmunol,2003,111 (5): 1032-1040.
    [206]HesseM,ModolellM,LaFlammeAC,etal Differential regulation of nitricoxide synthase-2 and arginase-1 by type1/type2 cytokinesinvivo:granulomatous pathologyis shaped by the pattern of L-arginine metabolism[J]. JImmunol, 2001,167(11):6533-6544.
    [207]KupermanDA, HuangX, KothLL,etal Directeffects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucusover production in asthma[J].NatMed,2002,8(8):885-889.
    [208]陈敏,STAT6及其基因多态性与支气管哮喘,国外医学呼吸系统分册,2005,25(4),258.
    [209]MillerRL,EppingerTM,McConnellD,etal.Analysis ocytokine signaling inpatients with extrinsic asthma anhyperimmunogiobulinE. Allergy ClinImmunol, 1998, 102(3):503-511.
    [210]AkimotoT,NumataF,TamuraM,etal.Abrogationof bronchia eosinophilic inflammation and airway hyperreactivity in signal transducers andactivators of transcription (STAT)6-deficien mice.ExpMed,1998, 187(9): 1537-1542.
    [211]PerezGM,MeloM,KeeganAD,etal.Aspirin and salicylate inhibit thelL-4 and IL-13 induced activation of STAT6. Immunol,2002,168(3): 1428-1434.
    [212]贺石林,王键,王净主编,中医科研设计与统计学,湖南:湖南科学技术出版社,2001第1版:48.
    [213]苗会,薛全福,庄逢源等,哮喘大鼠动物模型的制备[J],基础医学与临床,1998,18(1):72-78.
    [214]Renzi PM, Olivenstein R, Martin J G, et al. Inflammatory cell population in the airway and Parenchyma after antigen challenge in rat. Am Rev Respir Dis, 1993, 147:967.
    [215]申洪,免疫组织化学染色定量方法研究,中国组织化学与细胞化学杂志,1995,4(1):89292.
    [216]Behera AK,Kumar M,Lochey RF, etal.Adenovirusmediated interferon gamma gene therapy for allergic asthma:involvement of interleukin 4 and STAT6 signaling. Humgene Ther,2002,13,1697-1709.
    [217]Hoogan SP, Foster PS,Tan X,etal.Mucosalil 12gene delivery inhibits allergic airways diserse and restores local antiviral immunity.Eur J Immunol, 1998,28: 413-423.
    [218]YumikoK,Guell FW, Kline JN,etal.Gene transfer inhibits pulmonary allergic responses in mice.J Immunol, 1998,161:1074-1077.
    [219]Koller.Anidensenueleicacid the effective tools to studying gene function.Tyend Pharmae Sci,2000,21(4):142-148.
    [220]Duetsch G. Illing T.Loesgen S.etal.STAT6 as an asthmacandidate gene: polymorph-hism—screening association and haplotype analysis in a caucusian sibpair study. Hum Mol Gent,2002,11(6):613-621.
    [221]Lilly CM, Nakamura H,Belostotsky OI, etal. Eotaxin expression after segmental allergen challenge in subjects with atopic asthma. Am J Respir Crit Care Med, 2001,163,1669-1675.
    [222]张雷等,氨茶碱对哮喘大鼠肺内eotanxin表达的影响,第三军医大学学报,2005,27(17):1763—1765.
    [223]Zimmermann N, Daughter BL, Stark JM, Rothenberg ME, Melecular analysis of CCR-3 events in eosinophilic cells [J] Immunol, 2000:164(2):1055-1064[224]A SANO k, Nakamura M, Oguma T,Fukunage K, Matsubara H, Shiomi T, Ishizaka, Yamaguchi K, Kanazama M, differential expression of CCR3 ligand mrna in guinea pig lungs during allergen-induced inflammation [J]. Inflamm Res, 2001:50(12):625-630.
    [225]Lukacs NW, Role of chemokines in the pathogenesis of asthma [J] Nature Rew Immunol, 2001,1(2):108-116.
    [226]Renauld JC, New insights into the role of cytokines in asthma[J] J Clin Pathol 2001;54(8):577-589.
    [227]高晔珩等,麻黄研究进展,陕西中医学院学报,2003,39(3):308-314.
    [228]骆和生,《中药与免疫》,广州:广东科技出版社,1982,3.
    [229]Takami K,Takuwa N,Okazaki,etal.Interferon-γ Inhibits hepatocyte growth Factor stimulated cell proliferation of human bronchial epithelial cells[J].Am J Respir Cell Mol Boil,2002,26(9):231-238.
    [230]Liy, Wang L H,Sheng L.Study on trachea of uineapig of ziwan and gancao [J]. Inforn Tradit Chin Med,1999,16(4):47-48

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700