基于仲景“温化痰饮”理论探讨穴位敷贴治疗过敏性哮喘的效应机制
|
摘要
过敏性哮喘是一种由多种炎性细胞参与的气道慢性炎症性疾病,发病机制复杂。中医认为属“哮证”范畴,痰饮在其发生发展过程中占据主导作用。仲景《金匮要略·痰饮咳嗽病脉证并治篇》中提出“病痰饮者,当以温药和之”的治疗痰饮的总则,对痰饮的内治和外治均具有指导意义。本研究通过建立过敏性哮喘动物模型,在温化痰饮原则指导下,运用穴位敷贴这一临床常用且疗效确切的外治手段进行干预,探讨穴位敷贴治疗哮喘的效应机制,希望能为外治法领域的基础研究拓宽一些思路。
目的：通过观察以温化痰饮立法的穴位敷贴对过敏性哮喘豚鼠肺组织嗜酸性粒细胞凋亡情况、凋亡相关基因bax和bcl-2表达情况,血清白介素-4和y-干扰素的含量变化以及转录因子T-bet和GATA-3mRNA的表达情况的影响,初步探索穴位敷贴对过敏性哮喘气道炎症的作用机理。
方法：将Hartley豚鼠30只随机分为正常组、模型组、穴位敷贴组、非穴位敷贴组、阳性对照组,每组6只。采用卵蛋白腹腔注射致敏后呼吸道吸入激发法制备哮喘豚鼠模型。于造模成功次日给药,穴位敷贴组取肺俞、膻中、定喘穴进行敷贴,敷贴药物选取白芥子、麻黄、细辛、甘遂按一定比例以生姜汁调和,每次敷贴4h,每日1次,连续敷贴10天；阳性对照组以氨茶碱药饼敷贴,取穴部位及敷贴方法同穴位敷贴组；非穴位敷贴组取肺俞、膻中、定喘穴旁开1cm处,敷贴方法同穴位敷贴组；正常组、哮喘模型组不予治疗。治疗结束后对各组豚鼠体重、行为表现进行观察,对肺组织切片进行HE染色观察病理改变；TUNEL法检测肺组织EOS凋亡,免疫组化法检测肺组织凋亡相关基因bax和bcl-2的表达；ELISA法检测血清IL-4和IFN-γ的含量,RT-PCR方法检测转录因子T-bet和GATA-3mRNA的表达情况。所测数据均以均值加减标准差(X±s)表示,采用SPSS18.0统计软件分析数据,组间数据比较采用方差分析,P<0.05为差异有统计学意义。
实验结果
1.穴位敷贴对各组豚鼠一般情况及病理学的影响
穴位敷贴治疗后,穴位组、非穴位组体重较模型组有不同程度增加,行为学评分较模型组有明显降低。HE染色显示,模型组可见：气道粘膜充血水肿,大量炎性细胞浸润,穴位敷贴组、非穴位敷贴组、阳性对照组与模型组相比,上述改变明显减轻。
2.穴位敷贴对哮喘豚鼠EOS凋亡的影响
穴位组、非穴位组、阳性对照组EOS计数与模型组相比,均明显下降,三组EOS凋亡指数与模型组相比显著增加(P<0.01)；穴位组、非穴位组、阳性对照组bcl-2表达均较模型组下降,各组bax表达均较模型组上升,且统计学差异显著(P<0.01)。
3.穴位敷贴对哮喘豚鼠免疫调节机制
穴位组、非穴位组、阳性对照组血清IL-4含量较模型组显著下降,穴位组明显低于非穴位组(P<0.01)；穴位组、非穴位组、阳性对照组血清IFN-y含量较模型组显著上升,穴位组明显高于非穴位组(P<0.01)。
结论
1.以温化痰饮治法为指导,运用穴位敷贴治疗过敏性哮喘可以获得较好的疗效。
2.穴位敷贴可以改善发作期哮喘豚鼠的症状,减轻气道炎症反应。
3.穴位敷贴可以通过上调bax的表达并抑制bcl-2(?)勺表达,达到促进EOS凋亡的目的。
4.穴位敷贴能够通过调节转录因子T-bet和GATA-3的表达,从而影响细胞因子IL-4和IFN-y的分泌情况,纠正Thl/Th2失衡状态。
Allergic asthma is a chronic inflammatory disease of the airways which involves a variety of inflammatory cells and has complicated pathogenesis. Chinese traditional medicine considers it as a "xiao" category. Phlegm retention plays a dominant role in the development of its process. Zhongjing proposed the general principle that when one has phlegm retention, one should be treated with warm herbs, which gave lots of guidances to both internal and externaltreatments. Under this guidance, we discuss the effect mechanisms of acupoint application on established animal model of asthma, hoping to broaden the field of basic research for external treatment.
Objective By observing eosinophil apoptosis, expressions of apoptosis-related genes bax and bcl-2in lung tissue of allergic asthma guinea pigs, changes of serum interleukin-4and IFN-y contents, as well as the expressions of transcription factors T-betmRNA and GATA-3mRNA, we will preliminarily explore the effcet mechanisms of point application to airway inflammation in allergic asthma.
Methods30Hartley guinea pigs were randomly divided into normal group, model group, acupoint Application group, non-acupoint application group and positive control group, six for each group. Inhalation and intraperitoneal injection of ovalbumin sensitization were carried out to estabilish guinea pig model of allergic asthma. The second day of successful modeling, animals in point application group were treated by placing Chinese medicine at the point Feishu xue、danzhong xue and Dingchuan xue for4hours a day,lasting for10days in all. Animals in positive control group were treated with aminophylline applicator in the same way as point application group. Animals in non-acupoint applicator group were treated with drugs at the places lcm next to Feishu, danzhong and Dinchuan. Points applicator group.Normal group and asthma model group were not treated. At the end of treatment, we observed animals'weight variation, behaviors and HE staining pathological changes of lung tissue sections.we used Tunel assay to test EOS apoptosis, immunohistochemical assay to test the expressions of apoptosis re-lated genes bax and bcl-2in lung tissue.We detected the content of serum IL-4and IFN-y by ELISA method and adopted RT-PCR to detect expressions of transcription factors T-bet and GATA-3mRNA. All data were shown in the form of(x±s) and analyzed with one-way ANOVA by SPSS18.0,a=0.05.
Results
1. Influences on general situation and pathological changes in each group of guinea pigs
Compared with the model group, weights of acupoint application acupoint group and non-acupoint group increased to different degrees, and the behavioral score significantly reduced HE staining showed that in model group, bronchial mucosa epithelial cells fell off, goblet cells increased and inflammatory cells infiltrated, which took a turn for the better in acupoint application group, non-acupoint applicator group and positive control group.
2. Influences on EOS apoptosis in guinea pigs
Compared to model group, EOS count in positive control group, acupoint group and non-acupoint group, were significantly decreased, but EOS apoptotic index of these three groups showed a remarkable increase.The expression of bcl-2in acupoint group, non-acupoint group and positive control group decreased compared with model group, and the bax expression rose with statistically significant difference.
3. Immune adjustment mechanisms of acupoint application to allergic asthma
In acupuncture point group, non-acupuncture group and positive control group, the serum IL-4contents dropped significantly compared with model group.In acupuncture point group, non-acupuncture group and positive control group, the serum IFN-gamma increased significantly compared with the model group, and that of acupuncture group was more higher than acupuncture group.
Conclusions
1. Guided by the phlegm treatment, using acupoint sticking therapy for allergic asthma can achieve good effects.
2. Acupoint application can improve the symptoms of the acute episode of asthma, and relieve the airway inflammation.
3. Acupoint application can increase the expression of bax and suppress that of bcl-2, to achieve the goal of promoting EOS apoptosis.
4. Acupoint application can correct the Thl/Th2imbalance state by regulating the expressions of transcription factors T-bet and GATA-3, which affect the secretion of IL-4and IFN-γ.
目的：通过观察以温化痰饮立法的穴位敷贴对过敏性哮喘豚鼠肺组织嗜酸性粒细胞凋亡情况、凋亡相关基因bax和bcl-2表达情况,血清白介素-4和y-干扰素的含量变化以及转录因子T-bet和GATA-3mRNA的表达情况的影响,初步探索穴位敷贴对过敏性哮喘气道炎症的作用机理。
方法：将Hartley豚鼠30只随机分为正常组、模型组、穴位敷贴组、非穴位敷贴组、阳性对照组,每组6只。采用卵蛋白腹腔注射致敏后呼吸道吸入激发法制备哮喘豚鼠模型。于造模成功次日给药,穴位敷贴组取肺俞、膻中、定喘穴进行敷贴,敷贴药物选取白芥子、麻黄、细辛、甘遂按一定比例以生姜汁调和,每次敷贴4h,每日1次,连续敷贴10天；阳性对照组以氨茶碱药饼敷贴,取穴部位及敷贴方法同穴位敷贴组；非穴位敷贴组取肺俞、膻中、定喘穴旁开1cm处,敷贴方法同穴位敷贴组；正常组、哮喘模型组不予治疗。治疗结束后对各组豚鼠体重、行为表现进行观察,对肺组织切片进行HE染色观察病理改变；TUNEL法检测肺组织EOS凋亡,免疫组化法检测肺组织凋亡相关基因bax和bcl-2的表达；ELISA法检测血清IL-4和IFN-γ的含量,RT-PCR方法检测转录因子T-bet和GATA-3mRNA的表达情况。所测数据均以均值加减标准差(X±s)表示,采用SPSS18.0统计软件分析数据,组间数据比较采用方差分析,P<0.05为差异有统计学意义。
实验结果
1.穴位敷贴对各组豚鼠一般情况及病理学的影响
穴位敷贴治疗后,穴位组、非穴位组体重较模型组有不同程度增加,行为学评分较模型组有明显降低。HE染色显示,模型组可见：气道粘膜充血水肿,大量炎性细胞浸润,穴位敷贴组、非穴位敷贴组、阳性对照组与模型组相比,上述改变明显减轻。
2.穴位敷贴对哮喘豚鼠EOS凋亡的影响
穴位组、非穴位组、阳性对照组EOS计数与模型组相比,均明显下降,三组EOS凋亡指数与模型组相比显著增加(P<0.01)；穴位组、非穴位组、阳性对照组bcl-2表达均较模型组下降,各组bax表达均较模型组上升,且统计学差异显著(P<0.01)。
3.穴位敷贴对哮喘豚鼠免疫调节机制
穴位组、非穴位组、阳性对照组血清IL-4含量较模型组显著下降,穴位组明显低于非穴位组(P<0.01)；穴位组、非穴位组、阳性对照组血清IFN-y含量较模型组显著上升,穴位组明显高于非穴位组(P<0.01)。
结论
1.以温化痰饮治法为指导,运用穴位敷贴治疗过敏性哮喘可以获得较好的疗效。
2.穴位敷贴可以改善发作期哮喘豚鼠的症状,减轻气道炎症反应。
3.穴位敷贴可以通过上调bax的表达并抑制bcl-2(?)勺表达,达到促进EOS凋亡的目的。
4.穴位敷贴能够通过调节转录因子T-bet和GATA-3的表达,从而影响细胞因子IL-4和IFN-y的分泌情况,纠正Thl/Th2失衡状态。
Allergic asthma is a chronic inflammatory disease of the airways which involves a variety of inflammatory cells and has complicated pathogenesis. Chinese traditional medicine considers it as a "xiao" category. Phlegm retention plays a dominant role in the development of its process. Zhongjing proposed the general principle that when one has phlegm retention, one should be treated with warm herbs, which gave lots of guidances to both internal and externaltreatments. Under this guidance, we discuss the effect mechanisms of acupoint application on established animal model of asthma, hoping to broaden the field of basic research for external treatment.
Objective By observing eosinophil apoptosis, expressions of apoptosis-related genes bax and bcl-2in lung tissue of allergic asthma guinea pigs, changes of serum interleukin-4and IFN-y contents, as well as the expressions of transcription factors T-betmRNA and GATA-3mRNA, we will preliminarily explore the effcet mechanisms of point application to airway inflammation in allergic asthma.
Methods30Hartley guinea pigs were randomly divided into normal group, model group, acupoint Application group, non-acupoint application group and positive control group, six for each group. Inhalation and intraperitoneal injection of ovalbumin sensitization were carried out to estabilish guinea pig model of allergic asthma. The second day of successful modeling, animals in point application group were treated by placing Chinese medicine at the point Feishu xue、danzhong xue and Dingchuan xue for4hours a day,lasting for10days in all. Animals in positive control group were treated with aminophylline applicator in the same way as point application group. Animals in non-acupoint applicator group were treated with drugs at the places lcm next to Feishu, danzhong and Dinchuan. Points applicator group.Normal group and asthma model group were not treated. At the end of treatment, we observed animals'weight variation, behaviors and HE staining pathological changes of lung tissue sections.we used Tunel assay to test EOS apoptosis, immunohistochemical assay to test the expressions of apoptosis re-lated genes bax and bcl-2in lung tissue.We detected the content of serum IL-4and IFN-y by ELISA method and adopted RT-PCR to detect expressions of transcription factors T-bet and GATA-3mRNA. All data were shown in the form of(x±s) and analyzed with one-way ANOVA by SPSS18.0,a=0.05.
Results
1. Influences on general situation and pathological changes in each group of guinea pigs
Compared with the model group, weights of acupoint application acupoint group and non-acupoint group increased to different degrees, and the behavioral score significantly reduced HE staining showed that in model group, bronchial mucosa epithelial cells fell off, goblet cells increased and inflammatory cells infiltrated, which took a turn for the better in acupoint application group, non-acupoint applicator group and positive control group.
2. Influences on EOS apoptosis in guinea pigs
Compared to model group, EOS count in positive control group, acupoint group and non-acupoint group, were significantly decreased, but EOS apoptotic index of these three groups showed a remarkable increase.The expression of bcl-2in acupoint group, non-acupoint group and positive control group decreased compared with model group, and the bax expression rose with statistically significant difference.
3. Immune adjustment mechanisms of acupoint application to allergic asthma
In acupuncture point group, non-acupuncture group and positive control group, the serum IL-4contents dropped significantly compared with model group.In acupuncture point group, non-acupuncture group and positive control group, the serum IFN-gamma increased significantly compared with the model group, and that of acupuncture group was more higher than acupuncture group.
Conclusions
1. Guided by the phlegm treatment, using acupoint sticking therapy for allergic asthma can achieve good effects.
2. Acupoint application can improve the symptoms of the acute episode of asthma, and relieve the airway inflammation.
3. Acupoint application can increase the expression of bax and suppress that of bcl-2, to achieve the goal of promoting EOS apoptosis.
4. Acupoint application can correct the Thl/Th2imbalance state by regulating the expressions of transcription factors T-bet and GATA-3, which affect the secretion of IL-4and IFN-γ.
引文
[1]Vercelli D. Gene environment interaetions in asthma and allergy:the end of the beginning?[J]. Curr OPin Allergy Clin Immunol,2010,10(2):145.
[2]Wang W, JJ Li, PS Foster, et al. Potential therapeutic targets forsteroid-resistant asthma[J]. Curr Drug Targets,2010,11(8):957-970.
[3]Piehavant, M, S.Goya, E.H. Meyer, et al., Ozone exposure in a mouse-nodel Induces airway hyPerreaetivity that requires the Presence of Natural killer T cells and IL-17[J]. J ExP Med,2008,205(2); 385-393.
[4]Johnston R. A., M. Zhu, Y.M.Rivera-Sanchez, et al. Allergie airway responses in Obese mice[J]. Am J Respir Crit Care Med,2007,176(7):650-658.
[5]Wang, X.S., A.Y Wu, P.S. Leung, et al., PGE suppresses excessive anti-IgE induced cysteinyl leucotrienes production in mast cells of Patients with aspirin exacerbated respiratory disease[J]. Allergy,2007,62(6): 620-627.
[6]Dryden D.M., C.H. Spooner M.K. Stickland, et al. Exercise-induced Broncho constriction and asthma[J]. Evid ReP Technol Assess(Full Rep),2010,189(6):154.
[7]Burden of Asthma Report, Global Initiativ for Asthma(GINA).Available from http://www.9inasthma.com.
[8]Masolin M, Fabiann D, Holtn S, etal. The global burden of asthma:executive summary of the GINA Dissemination Committee report[J].Allergy,2004,59(3):469.
[9]陈育智,王红玉,王海俊,等.中国儿童呼吸道及特应性疾病患病情况调查[J].中华结核和呼吸杂志[J],2003,26(3)：143.
[10]李明华,殷凯生,朱栓立主编.哮喘病学[M].北京：人民卫生出版社,1998：3.
[11]钱娟娟,马佳韵,周敏,等.上海市宝山区支气管哮喘患病率和危险因素调查[J].内科理论与实践,2011,6(2)：121-122.
[12]陈兴保,吴观陵,孙新,等.现代寄生虫病学[M].北京：人民军医出版社,2002,927-932.
[13]Kim S, Camargo CA Jr. Sex-race Differences in the relationship between obesity and asthma:the behavioral risk factor surveillance system.2000[J]. Ann, Epidemiol,2003,13(6):666-673.
[14]Guermonprez P, Valladeau J, Itvogel L, etal. Antigen presentation and T cell stimulation by dendritic cells[J]. J Annu Rev Immunol,2002,20(9):621-627.
[15]Steinman RM, Inaba K, Turley S, et al. Antigen capture processing, and presentation by dendritic cells: Recent cell bio-logical studies[J]. Hum Immunol,1999,60(9):562-567.
[16]Ingulli E, Mondino A, Khorus A, et al.In vivodiction of dendritic cell antigen presentation to CD4+T cells[J]. J Exp Med,1997,185(6):2133-2141.
[17]Upham JM. The role of dendritic cells in immune regulation and allergic airway inflammation[J]. Int Arch Allergy Immunol,2003,130(3):180-192.
[18]Vermaelen KY, Cataldo D, Tournoy K, et al.Matrix metalloproteinse-9 mediated dendritic cell recruitment into the airways is a critical step in a mousemodel of asthma[J]. J Immunol,2003,171(2): 1016-1022.
[19]Spears M, Mc Sharry C, Donnelly L, etal. Peripheral blood dendritic cell subtypes are significantly elevated in subjects with asthma[J]. Clin Exp Allergy,2011,41(5):665-672.
[20]黄建安,张腊娣,于葛华,等.共刺激分子B7-CD28/CD152在过敏性哮喘中的作用[J].江苏医药杂志,2003,29(11)：806-807.
[22]Mosmnna TR, Coffman RL. Thl and Th2 cell, different pattens of lymphokine secretion[J]. Annu Rev Immunol,1989,7(8):145-173.
[23]沈晓明,王卫平.儿科学[M].北京：人民卫生出版社,2009：266-267.
[24]O'GarraA, Arai N. The molecular basis of T helper 1 and T helper 2 cell dieffrentiation[J]. Trends Cell Biol,2000,10(12):542-550.
[25]SzaboSJ, KimST, CostaGL, etal. A novel transcription factor, T-bet directs Thl lineage commitment[J]. Cell,2000,100(17):655-669.
[26]Szabo SJ, Kim ST, Costa GL, et al. A novel transcription factor, T-bet, directs Thl lineage commitment[J]. Cell,2000,100(17):655-669.
[27]Lighvani AA, Frucht DM,Jankovic D, etal. T-bet is rapidly induced by interferon- gamma in lymPhoiod and myeloid cells[J]. Proc Natl Acad Sci USA,2001,98(26):15137-15142.
[28]ZhengW, FlavellRA.Transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene in CD4+Tcells[J].Cell,1997,89(4):587-596.
[29]Ho IC, Vohtees P, Marin N, etal. Human GATA-3:a lineage-restricted transcprition factor that regulates the expression of the T celle recptor α gene[J]. EMBOJ,1991,10(5):1187-1192.
[30]HayakawaY, SmythMJ. CD27 dissectsmature NK cells into twosubsetswith distinct responsiveness and migratory capacity [J]. J Immunol 2006,176(18):1517-1524.
[31]Piedimonte G.Contribution of neuroimmune mechanisma to airway inflammtion and remodeling during and after respiratory syncytial virusinfecation[J].Pediatr Infect Dis,2003,22(3):66-75.
[32]Blalock JE. A molecul arbasis forbidirectional communication between the immune and neuroendocrine systems [J]. Physiol Rev,1989,69(1):1-32.
[33]Nassenstein C, Kutschker J, TumesD, etal. Neuro-immune interac-tion in allergic asthma:role of neurotrophins[J]. Biochem SocTrans,2006,34(Pt4):591-593.
[34]Feng JT, Hu CP. Dysfunction of releasing adrenaline in asthma bynerve growth factor[J]. MedHypotheses,2005,65(6):1043-1046.
[35]Masuda K, Aota Y, Muehleman C, et al. A genome-wide search for asthma susceptibility loci in ethnically diverse populations. The collaborative study on the geneties of asthma(CSGA)[J]. Nat Geneties, 1997,15(3):389-392.
[36]Blumenthal MN, Banks SS, Bleecker R, et al. Collaborative studies on the genetics of asthma-National Heart, Lung and Blood Institute[J].Clin ExP Allergy,1995,25(SuPP12):29-32.
[37]Srivastava P, Helms PJ, Stewart D, et al.Association of CCR5Delta 32 with reduced risk of childhood but not adult asthma[J].Mol Biotechnol,2003,23(1):51-60.
[38]Yao TC, Kuo ML, See LC, et al. The RANTES promoter polymor-Phism:a genetic risk factor for near-fatal asthma in Chinese children[J].Thorax,2003,58(6):466-469.
[39]Yousefi S, Hoessli DC, Blaser K, et a.l Requirement of Lyn and Syktyrosine kinases for the prevention of apoptosisby cytokines in human eo-siophils [J]. J Exp Med,1996,183(4):1407-1414.
[40]BerroAI. PerryGA, AgrawalDK. Inereased expression and activation of CD30 induce apoptosis in human blood eosinophils[J].J Immunol,2004,173(3):2174-2183.
[41]Walsh GM, Williamson ML, Symon FA, et al. Ligation of CD60 induces apoptosis and cell death in human eosinophyils cultured with granulocyte-macrophage colony-stimulating factor[J]. Blood,1996,87(5): 2815.
[42]Dorscheid DR, Kimberly R. Apottosis of airway epithelial cells induced by corticosteroids[J]. Am J Respir Crit Care Med,2001,164(10):1939-1947.
[43]Rathmell JC, Thompson CB. The central effectors of cell death in the immune system[J]. Annu Rev Immunol,1999,17(2):781-828.
[44]Jang AS, Choi IS, Lee S, et al. Bcl-2 expression in sputum eosinophils in patients with acute asthma[J]. Thorax,2000,55(5):370-374.
[45]刘光伟,龚守良.细胞凋亡的线粒体调控机制与电离辐射[J].国外医学·放射医学核医学分册,2003：7(2)：90-93.
[46]Herr I. Debatin K. Cellular stress response and apoptosis in cancer therapy[J]. Blood,2001; 98(9); 2603-2604.
[47]牛兵占,陈志强,徐树楠等.黄帝内经[M].石家庄：河北科技出版社,1994：365.
[48][清]叶天士.临证指南医案[M].上海；上海科技出版,2000,345.
[49]廖世才.小儿哮喘活血化癖法治疗体会仁[J].江西中医药,1997,28(6)：33.
[50]方永奇,简柳军,刘立秋.心血管病痰证患者血液流变学及植物神经功能的变化[J].中西医结合杂志,1989,3(19)：536.
[51]刘永平.论痰瘀是支气管哮喘的根本[J].辽宁中医杂志,2012,9(34)：664.
[52]周仲瑛.哮喘杂谈[J].江苏中医,2000,21(18)：15.
[53]张伟,邵雨萌.再论哮喘从癖论治[J].湖南中医学院学报,2004,24(3)：24.
[54]董竞成,石志芸,沈自尹,等.大剂量皮质类固醇吸人加补肾中药治疗激素依赖性哮喘的临床研究[J],中国中西医结合杂志,1994,14(8)；458-461.
[55]柯新桥等.支气管哮喘从肾虚辨治[J].新中医,2008,4(40)：3.
[56]孟庆春等.内科疑难病中医治疗学[M].北京：中国医药科技出版社,2002：22.
[57]江忠,田菊,杨志斌,等.玉屏风颗粒对哮喘患儿T淋巴细胞亚群的影响[J].中成药,2000,22(3)：210-211.
[58]周志荣.复方太子参止咳益气散治疗支气管哮喘2180例疗效观察[J].中国民族医药杂志,2005(5)：12.
[59]柯新桥,范鹏,朱众林.支气管哮喘从肾虚辨治[J].新中医2008(4)：3-4.
[60]毛昌淳,吴敦序,方肇勤等.补肾定喘汤对哮喘大鼠肺组织β2肾上腺素能受体及β2受体mRNA表达的作用[J].中国中医基础医学杂志,2001,7(8)：17.
[61]许得盛.温阳法对哮喘患者组胺释放IgE作用的同步观察[J].中西医结合杂志,1988,8(6)：330.
[62]彭红星.陈陶后教授治疗小儿哮喘经验[J].山西中医,1995,6(2)：5.
[63]陈燕,张洪春,杨道文,等.晃恩祥教授“从风论治”哮病的学术思想研究[J].中医药管理杂志,2007,15(4)：281-282.
[64]张德新,潘丰满.从风痰调治哮病[J].四川中医,2005,23(12)：13-15.
[65]赵杜鹃.综合疗法治疗支气管哮喘86例临床观察[J].辽宁中医杂志,2010,37(1)：84-86.
[66]史锁芳,曹世宏,郝月琴,等.平喘合剂治疗支气管哮喘发作期的临床研究[J].中国中医药科技,2005,12(1)；6-8.
[67]孙增涛,刘恩顺,封继宏,等.支气管哮喘发作期中医证候调查及证素提取的初步研究[J].中医杂志,2008,49(8)：731-733.
[68]李丹萍,廖辉,徐杰,等.活血化瘀药物干预治疗慢性肺心病加重期的临床观察[J].中国中西医结合杂志,2004,4(5)：454-456.
[69]董秀兰,王丽清,马华欣.益气活血定喘方治疗小儿哮喘缓解期30例疗效观察[J].新中医,2008,40(3)：47-48.
[70]王明明,胡英同.汪受传从肺论治小儿哮喘缓解期的经验[J].辽宁中医杂志,2001,28(8)：466.
[71]邱平.清化平喘汤与杏白用治疗支气管哮喘45例[J].湖北中医杂志,2002,24(7)：331.
[72]龙学明,唐耀平,黄洁,等.补肺片对支气管哮喘缓解期患者CD4+、CD8+及IgE影响的临床研究 [J].新中医,2007,39(5)：27-28.
[73]夏永良,王彩霞.哮喘缓解期从脾论治机理的研究[J].中医药学刊,2003,21(7)：1194.
[74]刘自力,吴兆利.培土生金法治疗支气管哮喘(缓解期)35例临床观察[J].中医药导报,2006,12(1)：37-381.
[75]任国英.益气平喘汤治疗支气管哮喘(缓解期)临证研究[J].实用中医内科杂志,2008,12(2)：23-24.
[76]赵四林,范伏元,贺选玲,等.加味二仙丸治疗支气管哮喘缓解期疗效观察[J].中国中医药信息杂志,2006,13(5)：59-60.
[77]吴彬,俞建,王营,等.补肾中药对哮喘缓解期患儿Thl/Th2平衡的影响[J].中国中西医结合杂志,2007,27(4)：120-122.
[78]吴秀艳,秦爱东.从肝论治支气管哮喘[J].陕西中医,2005,26(1)：47-49.
[79]王利,赵虹,苑秀华,等.舒肝顺肺汤治疗支气管哮喘急性发作期临床观察[J].中国中医急症,2007,16(10)：1189-1190.
[80]李麟俊.中医药治疗支气管炎哮喘300例临床观察[J].国医论坛,1998,13(5)：31.
[81]张有志,聂惠民,张宁,等.桂枝加厚朴杏子汤加味对过敏性哮喘豚鼠肿瘤坏死因子、内皮素的影响[J].北京中医药大学学报,2000,23(2)：23-24.
[82]谭素娟.射干麻黄汤化裁方抗过敏性哮喘的实验研究[J].中医杂志,2000,41(5)：282.
[83]童舜华.小青龙汤和补肾定喘汤对哮喘大鼠肺组织p受体和cAMP水平的影响[J].中成药,1999,21(6)：304.
[84]阮岩,李笋,封彦蕾,等.小青龙汤和麻黄汤抗组胺作用[J].中药新药与临床药理,2006,17(2)：145-147.
[85]黎同明,王桂香,全世健等.麻杏石甘汤对哮喘模型小鼠氧自由基代谢的影响[J].广州中医药大学学报,2006,11(23)：500-502.
[86]张洁,崔应珉.僵蚕治疗哮喘[J].中医杂志,2009,50(8)：724.
[87]张子臻,李刚.郁金治疗咳嗽型哮喘[J].中医杂志,2009,50(3)：240.
[88]胡晓光,李昌崇,王素娥,等.哮喘TH1/TH2失衡及牛膝多糖和地塞米松的作用[J].浙江中西医结合杂志,2004,14(2)：77.
[89]张瑜,张忠德,邓屹琪,等.中药辛桂散敷脐治疗支气管哮喘缓解期45例[J].辽宁中医杂志,2007,34(4)：442-443.
[90]徐艳玲,宫成军.中药涌泉穴贴敷治疗支气管哮喘临床研究[J].实用中医内科杂志,2008,22(5)：3-4.
[91]伍世葵,曹伟云.内服补肾温肺胶囊联合哮喘膏穴位敷贴治疗支气管哮喘34例临床观察[J].中医药导报,2007,13(5)：36-37.
[92]施小敏,唐运涛,喻洪钢,等.儿哮散穴位敷贴治疗小儿哮喘临床研究[J].四川中医,2005,23(4)：65-66.
[93]付娆,赵文波.哮喘贴片治疗哮喘的研究[J].黑龙江中医药,2004(4)：9-10.
[94]李雁,葛兆希.子午流注纳子针法治疗哮喘30例疗效观察[J].时珍国医国药,2010,21(2)：424-425.
[95]张智龙,吉学群,薛莉,等.针刺治疗支气管哮喘急性发作期临床观察[J].中国针灸,2005,25(3)：158-160.
[96]万文蓉.温阳利气法针灸治疗哮喘30例临床观察[J].中国针灸,2001,21(11)：649-6501.
[97]王进法.梅花针治疗小儿支气管哮喘34例[J].针灸临床杂志,1996,12(10)：20.
[98]赵吉平,崔红生.温和灸治疗支气管哮喘缓解期36例疗效观察[J].中国民间疗法,2002,10(4)：21.
[99]王艳君,沈立杰,桑春霞.重组干扰素-丫穴位注射佐治儿童哮喘疗效观察[J].中国实用乡村医生杂志,2005,12(1)：34-35.
[100]高洪英,徐建勇.痰热清穴位注射治疗小儿支气管哮喘52例[J].时珍国医国药,2006,17(9)：1754-1755.
[101]徐建勇,高洪英.天突穴位注射治疗小儿支气管哮喘72例[J].中国针灸,2005,26(6)：416.
[102]刘良伦.清肺泄痰汤灌肠治疗小儿咳喘症[J].中国中医药现代远程教育,2008,6(2)：164.
[103]周志荣.中药直肠滴入治疗婴幼儿哮喘50例[J].浙江中医学院学报,2005,29(5)：44.
[104]王烈.婴童哮论[M].长春：吉林科学技术出版社,2001：194.
[105]周仲瑛.哮喘杂谈[J].江苏中医,2000,(8)：1-4.
[106]李杰.中医药对哮喘嗜酸性粒细胞凋亡及白细胞介素-5的研究概况[J].湖南中医学院学报,2002(2)：64-65.
[107]李杰.中医药对哮喘EOS凋亡及白细胞介素-5的研究概况[J].湖南中医学院学报,2002,2(2)：64-65.
[108]王平,田代志,张茂韩,等.肺虚痰阻大鼠巨噬细粘胞功能和附分子CDllb的表达研究[J].中医药学刊,2004,22(7)：1167-1195.
[109]李建保,田金娜.基于JAK/STAT信号通路对哮喘痰饮夙根潜伏与活化的理论探析[J].辽宁中医杂志,2011,38(7)：1337-1338.
[110]Mccusker CT, Wang Y, Shah J, et al.Inhibition of expefimental allergic airways disease by local application of a cellpenetrating dominant-negative STAT6 peptide[J]. J Immunol,2007,179 (4):2556-2564.
[111]施焕中,林江涛肺脏免疫学及免疫相关性疾病[M].北京：人民卫生出版社,2006：316-317.
[112]盛青,何建猷,周爱莲,等.雷公藤甲素对哮喘小鼠信号转导和转录激活因子6及Eotaxin表达的影响[J].国际呼吸杂志,2006,26(1)：12-15.
[113]王永霞,李丰涛.从痰饮论治慢性心力衰竭的思路与方法[J].中西医结合心脑血管病杂志,2011,1(9)：111-112.
[114]高卫卫,姚昶.温阳化痰法治疗桥本氏甲状腺炎60例临床观察[J].云南中医中药杂志,2010,31(1)：18-19.
[115]陈仲杰,吴中朝,王巧妹,等.高脂血症痰饮病机及“温灸和之”治法探析[J].中医杂志,2012,53(9)：1460-1463.
[116]柴可夫,谷英敏.治疗溃疡性结肠炎当“以温药和之”[J].中华中医药学刊,2010,28(6),1139-1141.
[117]谢伟,陆满文.细辛挥发油的化学与药理作用[J].宁夏医学杂志,1995,17(2)：121-124.
[118]张会宗,张世良,李伟博,等.细辛药材不同部位GC指纹谱分析及药材含量测定[J].中华中医药学刊,2009,27(12)：2612-2615.
[119]张学梅,刘凡亮,梁文波,等.白芥子提取物的镇咳、祛痰及平喘作用研究[J].中草药,2003,34(7)：635.
[120]高雪,曲敬来.中药穴位贴敷治疗支气管哮喘机理探讨[J].针灸临床杂志,1998,14(8)：36.
[121]聂淑琴,李泽琳,梁爱华,等.炮制对甘遂、牛膝、苦杏仁特殊毒性及药效的影响[J].中国中药杂志,1996,21(3)：153.
[122]李嗣英.甘遂对小鼠免疫功能的影响[J].中国药理通讯,1989,6(2)：10.
[123]Satoshi N, Susumu K, Chisei R.3-O-(2,3-Dimethylbutanoyl)-13-O-decanoylingenol from Euphorbia kansui Suppresses IgE-Mediated Mast Cell Activation[J].VoBiol PharmBull,2006,29(2):286-290.
[124]刘善庭,辛勤,李建美,等.生姜对呼吸平滑肌作用的实验研究[J].济宁医学院学报,1996,19(4)：26-27.
[125]张压西,陈友梅.针刺肺俞穴改善肺功能时效关系研究[J].中国针灸,1997,3(10)：581-582.
[126]胡志光等.针刺对支气管哮喘患者T淋巴细胞亚群和IL-4的影响[J].中国针灸,1999,19(2)：111.
[127]孙占玲,王伟.膻中穴埋线对哮喘豚鼠气道炎症的影响[J].浙江中医杂志,2007,7(42)：392-393
[128]刘幸平,许惠琴,狄留庆.定喘穴贴膏对过敏性哮喘豚鼠SOD、MDA、NO和NOS的影响[J].中医研究,2001,5(3)：9.
[129]Palmans E, Kips JC, Pauwels PA. Prolonged allergen exposure induces structural airway changes in sensitized rats[J]. Am J Respir Crit Care Med,2000,161(2):627-635.
[130]李惠民,赵顺英,江载芳.支气管上皮细胞在大鼠哮喘模型气道炎症和重塑中的作用[J].中国实用儿科杂志,2007,22(7)：526-530.
[131]李忠仁.实验针灸学[M].北京：中国中医药出版社,2003：325-326.
[132]刘金保,钟南山,李树浓,等.PPD对豚鼠实验性哮喘气道炎症的作用[J].免疫学杂志,2002,18(5)：350-352.
[133]黄艳,刘鑫,戴爱国,等.柴朴汤对卵蛋白诱导豚鼠哮喘的干预作用与对核因子-JB的影响[J].中医药导报,2007,13(6)：1-3.
[134]Schuster M, Tscherning T, Krug N, et al. Lymphocytes migrate from the blood into the bronchoalveolar lvage and lung parenchyma in the asthma model of the brown-norway rat[J]. Am J Respir Care Med,2000, 161(2):558-566.
[135]Sedgwiek J B. Vrtis R F, Jansen K J, et al. Peripheral blood Eosinophils from patients with allergic asthma contain increased intracellular eosinophil-derived neurotoxin[J]. J Allergy Clin Immunol,2004, 114(5):568-574.
[136]Southam DS, W idmerN, EllisR,et al. Increased eosinophil-lineage committed progenitors in the lung of allergen-challenged mice[J]. JAllergy Clin Immunol,2005,115(1):95-102.
[137]Ravensberg A J, Ricciardolo F L, van Schadewiik A, et al.Eotaxin-2 and eotaxin-3 expression is associated with Persistent eosinophilic bronchial inflammation in patients with asthma after allegen challenge[J]. J Allery Clin Immunol,2005,115(3):779-785.
[138]Stern M, Meagher L, Savil J, et al. Apoptosis in human eosinophils:Programmed cell death in the eosinophil leads to Phagocytosis by Macrophages and is modulated by IL-5[J]. J Immunol,1992,148(4): 3543-3549.
[139]Inman MD, Ellis R, Wattie J, et a.l.Allergen-induced increase in airway responsiveness, airway eosinophilia, and bone-marroweosinophil progenitors inmice[J].Am JRespirCellMolBiol,1999,21:473-479..
[140]Kitagaki K, Niwa S, Hoshiko K, et al. Augmentation of apoptosis in bronchal exuded rat eosinophils by cyclosporine A[J]. Biochem Bi-ophys Res Comnfun,1996,222(1):71-77.
[141]Letuve S, Druilhe A, Grandsaigne M, et al. Involvement of cas-pases and of mitochondria in Fas ligation-induced eosinophil apoptosis:modulation by interleukin-5 and interferon-gamma. J Leukoc Biol, 2001,70(4):767-775.
[142]Berro A I, Perry G A, Agrawal D K. Inereased expression and activation of CD30 induce apoptosis in human blood eosinophils. J Immunol,2004,173(5):2174-2183.
[143]Simon HU.Int Arch Allergy Immunl,1997,113(6):206-208.
[144]Chami M, Prandini A, Campanella M, et al. Bcl-2 and Bax exert opposing effects on Ca2+ signaling, which do not depend on their putative poreforming region[J]. J Biol Chem,2004,279(8):54-58.
[145]Youle R J, Strasser A. The Bcl-2 protein family:opposing activities that mediate cell death[J]. Nat Rev Mol Cell Biol,2008,9(1):47-59.
[146]Rathmell J C, Thompson C B. The central effectors of cell death in the immune system [J]. Annu Rev Immunol,1999,17(2):781-828.
[147]Voehringer D W, Meyn RE. Redox aspects of Bcl-2 function [J]. Antioxid Redox Signal,2000,22(2): 37-501.
[148]Dorscheid D R, Kimberly R. Apottosis of airway epithelial cells induced by corticosteroids[J]. Am J Respir Crit Care Med,2001,164(10):1939-1947.
[149]刘光伟,龚守良.细胞凋亡的线粒体调控机制与电离辐射[J].国外医学·放射医学核医学分册,2003：7(2)：90-93.
[150]Herr I, Debatin K. Cellular stress response and apoptosis in cancer therapy [J]. Blood,2001; 98(9): 2603-2604.
[151]Rudge E U, CutlerA J, Pritehard N R, et al. Interleukin 4 reduces expression of inhibitory receptors on B cells and abolishes CD22 and Fc gamma Rll-mediated B cell suppression[J].The Journal of ExP erimental Medieine,2009,195(8):1079-1085.
[152]Riifo V Y, Picthford S, Spina D. Cytokines in airway inflammation[J]. Int J Biochem Cell Biol,2000, 32(8):833-853.
[153]Hofstra C L, VanArk J, Hofiman G, et al. Different effeets of endogenous and esogenous interferon gamma on immunoglobulinE, cellular infiltration, and aiway respinsivenessin amurine model of allergy asthma[J]. Am J Respir Cell MoL Biol,1998,19(5):82-83.
[154]Finotto S, Neurath M F, Glickman J N, et al. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet[J]. Science,2002,295(3):336-338.
[155]Szabo S J, Kim S T, Costa G L, et al. A novel transcription factor, T-bet, directs Thl lineage commitment[J].Cell,2000,100(6):655-669.
[156]Assanasen P, Baroody F M, Naureckas E, et al.The nasal Passage of subjects with asthma has a decreased ability to warm and humidify inspired air[J]. Am J Respir Crit Care Med,2001,164:1640-1646.
[157]Nakamura Y, Ghaffar O, O livenstein R, et al. Gene expression of the GATA-3 transcription factors is increased in atopic asthma[J]. J Allergy C lin Immunol,1999,103(9):215-222.
[158]Zheng W, Flavell R A. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4+T cells[J]. Cell,1997,89(4):587-596.
[159]Dong L, Chen M, Zhang Q, et al. T-bet/GA-TA-3 ratio is a surrogate measure of Th1/Th2 cytokine profiles and may be novel targets for CpGODN treatment in asthma patients[J]. Chin Med J (Engl),2006, 119(16):1396-1399.
[160]刘春涛,王刚,罗凤鸣,等.支气管哮喘患者Th2细胞过度分化与转录因子T-bet和GATA-3的调控作用[J].中华结核和呼吸杂志,2004,6(27)：398-399.
[2]Wang W, JJ Li, PS Foster, et al. Potential therapeutic targets forsteroid-resistant asthma[J]. Curr Drug Targets,2010,11(8):957-970.
[3]Piehavant, M, S.Goya, E.H. Meyer, et al., Ozone exposure in a mouse-nodel Induces airway hyPerreaetivity that requires the Presence of Natural killer T cells and IL-17[J]. J ExP Med,2008,205(2); 385-393.
[4]Johnston R. A., M. Zhu, Y.M.Rivera-Sanchez, et al. Allergie airway responses in Obese mice[J]. Am J Respir Crit Care Med,2007,176(7):650-658.
[5]Wang, X.S., A.Y Wu, P.S. Leung, et al., PGE suppresses excessive anti-IgE induced cysteinyl leucotrienes production in mast cells of Patients with aspirin exacerbated respiratory disease[J]. Allergy,2007,62(6): 620-627.
[6]Dryden D.M., C.H. Spooner M.K. Stickland, et al. Exercise-induced Broncho constriction and asthma[J]. Evid ReP Technol Assess(Full Rep),2010,189(6):154.
[7]Burden of Asthma Report, Global Initiativ for Asthma(GINA).Available from http://www.9inasthma.com.
[8]Masolin M, Fabiann D, Holtn S, etal. The global burden of asthma:executive summary of the GINA Dissemination Committee report[J].Allergy,2004,59(3):469.
[9]陈育智,王红玉,王海俊,等.中国儿童呼吸道及特应性疾病患病情况调查[J].中华结核和呼吸杂志[J],2003,26(3)：143.
[10]李明华,殷凯生,朱栓立主编.哮喘病学[M].北京：人民卫生出版社,1998：3.
[11]钱娟娟,马佳韵,周敏,等.上海市宝山区支气管哮喘患病率和危险因素调查[J].内科理论与实践,2011,6(2)：121-122.
[12]陈兴保,吴观陵,孙新,等.现代寄生虫病学[M].北京：人民军医出版社,2002,927-932.
[13]Kim S, Camargo CA Jr. Sex-race Differences in the relationship between obesity and asthma:the behavioral risk factor surveillance system.2000[J]. Ann, Epidemiol,2003,13(6):666-673.
[14]Guermonprez P, Valladeau J, Itvogel L, etal. Antigen presentation and T cell stimulation by dendritic cells[J]. J Annu Rev Immunol,2002,20(9):621-627.
[15]Steinman RM, Inaba K, Turley S, et al. Antigen capture processing, and presentation by dendritic cells: Recent cell bio-logical studies[J]. Hum Immunol,1999,60(9):562-567.
[16]Ingulli E, Mondino A, Khorus A, et al.In vivodiction of dendritic cell antigen presentation to CD4+T cells[J]. J Exp Med,1997,185(6):2133-2141.
[17]Upham JM. The role of dendritic cells in immune regulation and allergic airway inflammation[J]. Int Arch Allergy Immunol,2003,130(3):180-192.
[18]Vermaelen KY, Cataldo D, Tournoy K, et al.Matrix metalloproteinse-9 mediated dendritic cell recruitment into the airways is a critical step in a mousemodel of asthma[J]. J Immunol,2003,171(2): 1016-1022.
[19]Spears M, Mc Sharry C, Donnelly L, etal. Peripheral blood dendritic cell subtypes are significantly elevated in subjects with asthma[J]. Clin Exp Allergy,2011,41(5):665-672.
[20]黄建安,张腊娣,于葛华,等.共刺激分子B7-CD28/CD152在过敏性哮喘中的作用[J].江苏医药杂志,2003,29(11)：806-807.
[22]Mosmnna TR, Coffman RL. Thl and Th2 cell, different pattens of lymphokine secretion[J]. Annu Rev Immunol,1989,7(8):145-173.
[23]沈晓明,王卫平.儿科学[M].北京：人民卫生出版社,2009：266-267.
[24]O'GarraA, Arai N. The molecular basis of T helper 1 and T helper 2 cell dieffrentiation[J]. Trends Cell Biol,2000,10(12):542-550.
[25]SzaboSJ, KimST, CostaGL, etal. A novel transcription factor, T-bet directs Thl lineage commitment[J]. Cell,2000,100(17):655-669.
[26]Szabo SJ, Kim ST, Costa GL, et al. A novel transcription factor, T-bet, directs Thl lineage commitment[J]. Cell,2000,100(17):655-669.
[27]Lighvani AA, Frucht DM,Jankovic D, etal. T-bet is rapidly induced by interferon- gamma in lymPhoiod and myeloid cells[J]. Proc Natl Acad Sci USA,2001,98(26):15137-15142.
[28]ZhengW, FlavellRA.Transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene in CD4+Tcells[J].Cell,1997,89(4):587-596.
[29]Ho IC, Vohtees P, Marin N, etal. Human GATA-3:a lineage-restricted transcprition factor that regulates the expression of the T celle recptor α gene[J]. EMBOJ,1991,10(5):1187-1192.
[30]HayakawaY, SmythMJ. CD27 dissectsmature NK cells into twosubsetswith distinct responsiveness and migratory capacity [J]. J Immunol 2006,176(18):1517-1524.
[31]Piedimonte G.Contribution of neuroimmune mechanisma to airway inflammtion and remodeling during and after respiratory syncytial virusinfecation[J].Pediatr Infect Dis,2003,22(3):66-75.
[32]Blalock JE. A molecul arbasis forbidirectional communication between the immune and neuroendocrine systems [J]. Physiol Rev,1989,69(1):1-32.
[33]Nassenstein C, Kutschker J, TumesD, etal. Neuro-immune interac-tion in allergic asthma:role of neurotrophins[J]. Biochem SocTrans,2006,34(Pt4):591-593.
[34]Feng JT, Hu CP. Dysfunction of releasing adrenaline in asthma bynerve growth factor[J]. MedHypotheses,2005,65(6):1043-1046.
[35]Masuda K, Aota Y, Muehleman C, et al. A genome-wide search for asthma susceptibility loci in ethnically diverse populations. The collaborative study on the geneties of asthma(CSGA)[J]. Nat Geneties, 1997,15(3):389-392.
[36]Blumenthal MN, Banks SS, Bleecker R, et al. Collaborative studies on the genetics of asthma-National Heart, Lung and Blood Institute[J].Clin ExP Allergy,1995,25(SuPP12):29-32.
[37]Srivastava P, Helms PJ, Stewart D, et al.Association of CCR5Delta 32 with reduced risk of childhood but not adult asthma[J].Mol Biotechnol,2003,23(1):51-60.
[38]Yao TC, Kuo ML, See LC, et al. The RANTES promoter polymor-Phism:a genetic risk factor for near-fatal asthma in Chinese children[J].Thorax,2003,58(6):466-469.
[39]Yousefi S, Hoessli DC, Blaser K, et a.l Requirement of Lyn and Syktyrosine kinases for the prevention of apoptosisby cytokines in human eo-siophils [J]. J Exp Med,1996,183(4):1407-1414.
[40]BerroAI. PerryGA, AgrawalDK. Inereased expression and activation of CD30 induce apoptosis in human blood eosinophils[J].J Immunol,2004,173(3):2174-2183.
[41]Walsh GM, Williamson ML, Symon FA, et al. Ligation of CD60 induces apoptosis and cell death in human eosinophyils cultured with granulocyte-macrophage colony-stimulating factor[J]. Blood,1996,87(5): 2815.
[42]Dorscheid DR, Kimberly R. Apottosis of airway epithelial cells induced by corticosteroids[J]. Am J Respir Crit Care Med,2001,164(10):1939-1947.
[43]Rathmell JC, Thompson CB. The central effectors of cell death in the immune system[J]. Annu Rev Immunol,1999,17(2):781-828.
[44]Jang AS, Choi IS, Lee S, et al. Bcl-2 expression in sputum eosinophils in patients with acute asthma[J]. Thorax,2000,55(5):370-374.
[45]刘光伟,龚守良.细胞凋亡的线粒体调控机制与电离辐射[J].国外医学·放射医学核医学分册,2003：7(2)：90-93.
[46]Herr I. Debatin K. Cellular stress response and apoptosis in cancer therapy[J]. Blood,2001; 98(9); 2603-2604.
[47]牛兵占,陈志强,徐树楠等.黄帝内经[M].石家庄：河北科技出版社,1994：365.
[48][清]叶天士.临证指南医案[M].上海；上海科技出版,2000,345.
[49]廖世才.小儿哮喘活血化癖法治疗体会仁[J].江西中医药,1997,28(6)：33.
[50]方永奇,简柳军,刘立秋.心血管病痰证患者血液流变学及植物神经功能的变化[J].中西医结合杂志,1989,3(19)：536.
[51]刘永平.论痰瘀是支气管哮喘的根本[J].辽宁中医杂志,2012,9(34)：664.
[52]周仲瑛.哮喘杂谈[J].江苏中医,2000,21(18)：15.
[53]张伟,邵雨萌.再论哮喘从癖论治[J].湖南中医学院学报,2004,24(3)：24.
[54]董竞成,石志芸,沈自尹,等.大剂量皮质类固醇吸人加补肾中药治疗激素依赖性哮喘的临床研究[J],中国中西医结合杂志,1994,14(8)；458-461.
[55]柯新桥等.支气管哮喘从肾虚辨治[J].新中医,2008,4(40)：3.
[56]孟庆春等.内科疑难病中医治疗学[M].北京：中国医药科技出版社,2002：22.
[57]江忠,田菊,杨志斌,等.玉屏风颗粒对哮喘患儿T淋巴细胞亚群的影响[J].中成药,2000,22(3)：210-211.
[58]周志荣.复方太子参止咳益气散治疗支气管哮喘2180例疗效观察[J].中国民族医药杂志,2005(5)：12.
[59]柯新桥,范鹏,朱众林.支气管哮喘从肾虚辨治[J].新中医2008(4)：3-4.
[60]毛昌淳,吴敦序,方肇勤等.补肾定喘汤对哮喘大鼠肺组织β2肾上腺素能受体及β2受体mRNA表达的作用[J].中国中医基础医学杂志,2001,7(8)：17.
[61]许得盛.温阳法对哮喘患者组胺释放IgE作用的同步观察[J].中西医结合杂志,1988,8(6)：330.
[62]彭红星.陈陶后教授治疗小儿哮喘经验[J].山西中医,1995,6(2)：5.
[63]陈燕,张洪春,杨道文,等.晃恩祥教授“从风论治”哮病的学术思想研究[J].中医药管理杂志,2007,15(4)：281-282.
[64]张德新,潘丰满.从风痰调治哮病[J].四川中医,2005,23(12)：13-15.
[65]赵杜鹃.综合疗法治疗支气管哮喘86例临床观察[J].辽宁中医杂志,2010,37(1)：84-86.
[66]史锁芳,曹世宏,郝月琴,等.平喘合剂治疗支气管哮喘发作期的临床研究[J].中国中医药科技,2005,12(1)；6-8.
[67]孙增涛,刘恩顺,封继宏,等.支气管哮喘发作期中医证候调查及证素提取的初步研究[J].中医杂志,2008,49(8)：731-733.
[68]李丹萍,廖辉,徐杰,等.活血化瘀药物干预治疗慢性肺心病加重期的临床观察[J].中国中西医结合杂志,2004,4(5)：454-456.
[69]董秀兰,王丽清,马华欣.益气活血定喘方治疗小儿哮喘缓解期30例疗效观察[J].新中医,2008,40(3)：47-48.
[70]王明明,胡英同.汪受传从肺论治小儿哮喘缓解期的经验[J].辽宁中医杂志,2001,28(8)：466.
[71]邱平.清化平喘汤与杏白用治疗支气管哮喘45例[J].湖北中医杂志,2002,24(7)：331.
[72]龙学明,唐耀平,黄洁,等.补肺片对支气管哮喘缓解期患者CD4+、CD8+及IgE影响的临床研究 [J].新中医,2007,39(5)：27-28.
[73]夏永良,王彩霞.哮喘缓解期从脾论治机理的研究[J].中医药学刊,2003,21(7)：1194.
[74]刘自力,吴兆利.培土生金法治疗支气管哮喘(缓解期)35例临床观察[J].中医药导报,2006,12(1)：37-381.
[75]任国英.益气平喘汤治疗支气管哮喘(缓解期)临证研究[J].实用中医内科杂志,2008,12(2)：23-24.
[76]赵四林,范伏元,贺选玲,等.加味二仙丸治疗支气管哮喘缓解期疗效观察[J].中国中医药信息杂志,2006,13(5)：59-60.
[77]吴彬,俞建,王营,等.补肾中药对哮喘缓解期患儿Thl/Th2平衡的影响[J].中国中西医结合杂志,2007,27(4)：120-122.
[78]吴秀艳,秦爱东.从肝论治支气管哮喘[J].陕西中医,2005,26(1)：47-49.
[79]王利,赵虹,苑秀华,等.舒肝顺肺汤治疗支气管哮喘急性发作期临床观察[J].中国中医急症,2007,16(10)：1189-1190.
[80]李麟俊.中医药治疗支气管炎哮喘300例临床观察[J].国医论坛,1998,13(5)：31.
[81]张有志,聂惠民,张宁,等.桂枝加厚朴杏子汤加味对过敏性哮喘豚鼠肿瘤坏死因子、内皮素的影响[J].北京中医药大学学报,2000,23(2)：23-24.
[82]谭素娟.射干麻黄汤化裁方抗过敏性哮喘的实验研究[J].中医杂志,2000,41(5)：282.
[83]童舜华.小青龙汤和补肾定喘汤对哮喘大鼠肺组织p受体和cAMP水平的影响[J].中成药,1999,21(6)：304.
[84]阮岩,李笋,封彦蕾,等.小青龙汤和麻黄汤抗组胺作用[J].中药新药与临床药理,2006,17(2)：145-147.
[85]黎同明,王桂香,全世健等.麻杏石甘汤对哮喘模型小鼠氧自由基代谢的影响[J].广州中医药大学学报,2006,11(23)：500-502.
[86]张洁,崔应珉.僵蚕治疗哮喘[J].中医杂志,2009,50(8)：724.
[87]张子臻,李刚.郁金治疗咳嗽型哮喘[J].中医杂志,2009,50(3)：240.
[88]胡晓光,李昌崇,王素娥,等.哮喘TH1/TH2失衡及牛膝多糖和地塞米松的作用[J].浙江中西医结合杂志,2004,14(2)：77.
[89]张瑜,张忠德,邓屹琪,等.中药辛桂散敷脐治疗支气管哮喘缓解期45例[J].辽宁中医杂志,2007,34(4)：442-443.
[90]徐艳玲,宫成军.中药涌泉穴贴敷治疗支气管哮喘临床研究[J].实用中医内科杂志,2008,22(5)：3-4.
[91]伍世葵,曹伟云.内服补肾温肺胶囊联合哮喘膏穴位敷贴治疗支气管哮喘34例临床观察[J].中医药导报,2007,13(5)：36-37.
[92]施小敏,唐运涛,喻洪钢,等.儿哮散穴位敷贴治疗小儿哮喘临床研究[J].四川中医,2005,23(4)：65-66.
[93]付娆,赵文波.哮喘贴片治疗哮喘的研究[J].黑龙江中医药,2004(4)：9-10.
[94]李雁,葛兆希.子午流注纳子针法治疗哮喘30例疗效观察[J].时珍国医国药,2010,21(2)：424-425.
[95]张智龙,吉学群,薛莉,等.针刺治疗支气管哮喘急性发作期临床观察[J].中国针灸,2005,25(3)：158-160.
[96]万文蓉.温阳利气法针灸治疗哮喘30例临床观察[J].中国针灸,2001,21(11)：649-6501.
[97]王进法.梅花针治疗小儿支气管哮喘34例[J].针灸临床杂志,1996,12(10)：20.
[98]赵吉平,崔红生.温和灸治疗支气管哮喘缓解期36例疗效观察[J].中国民间疗法,2002,10(4)：21.
[99]王艳君,沈立杰,桑春霞.重组干扰素-丫穴位注射佐治儿童哮喘疗效观察[J].中国实用乡村医生杂志,2005,12(1)：34-35.
[100]高洪英,徐建勇.痰热清穴位注射治疗小儿支气管哮喘52例[J].时珍国医国药,2006,17(9)：1754-1755.
[101]徐建勇,高洪英.天突穴位注射治疗小儿支气管哮喘72例[J].中国针灸,2005,26(6)：416.
[102]刘良伦.清肺泄痰汤灌肠治疗小儿咳喘症[J].中国中医药现代远程教育,2008,6(2)：164.
[103]周志荣.中药直肠滴入治疗婴幼儿哮喘50例[J].浙江中医学院学报,2005,29(5)：44.
[104]王烈.婴童哮论[M].长春：吉林科学技术出版社,2001：194.
[105]周仲瑛.哮喘杂谈[J].江苏中医,2000,(8)：1-4.
[106]李杰.中医药对哮喘嗜酸性粒细胞凋亡及白细胞介素-5的研究概况[J].湖南中医学院学报,2002(2)：64-65.
[107]李杰.中医药对哮喘EOS凋亡及白细胞介素-5的研究概况[J].湖南中医学院学报,2002,2(2)：64-65.
[108]王平,田代志,张茂韩,等.肺虚痰阻大鼠巨噬细粘胞功能和附分子CDllb的表达研究[J].中医药学刊,2004,22(7)：1167-1195.
[109]李建保,田金娜.基于JAK/STAT信号通路对哮喘痰饮夙根潜伏与活化的理论探析[J].辽宁中医杂志,2011,38(7)：1337-1338.
[110]Mccusker CT, Wang Y, Shah J, et al.Inhibition of expefimental allergic airways disease by local application of a cellpenetrating dominant-negative STAT6 peptide[J]. J Immunol,2007,179 (4):2556-2564.
[111]施焕中,林江涛肺脏免疫学及免疫相关性疾病[M].北京：人民卫生出版社,2006：316-317.
[112]盛青,何建猷,周爱莲,等.雷公藤甲素对哮喘小鼠信号转导和转录激活因子6及Eotaxin表达的影响[J].国际呼吸杂志,2006,26(1)：12-15.
[113]王永霞,李丰涛.从痰饮论治慢性心力衰竭的思路与方法[J].中西医结合心脑血管病杂志,2011,1(9)：111-112.
[114]高卫卫,姚昶.温阳化痰法治疗桥本氏甲状腺炎60例临床观察[J].云南中医中药杂志,2010,31(1)：18-19.
[115]陈仲杰,吴中朝,王巧妹,等.高脂血症痰饮病机及“温灸和之”治法探析[J].中医杂志,2012,53(9)：1460-1463.
[116]柴可夫,谷英敏.治疗溃疡性结肠炎当“以温药和之”[J].中华中医药学刊,2010,28(6),1139-1141.
[117]谢伟,陆满文.细辛挥发油的化学与药理作用[J].宁夏医学杂志,1995,17(2)：121-124.
[118]张会宗,张世良,李伟博,等.细辛药材不同部位GC指纹谱分析及药材含量测定[J].中华中医药学刊,2009,27(12)：2612-2615.
[119]张学梅,刘凡亮,梁文波,等.白芥子提取物的镇咳、祛痰及平喘作用研究[J].中草药,2003,34(7)：635.
[120]高雪,曲敬来.中药穴位贴敷治疗支气管哮喘机理探讨[J].针灸临床杂志,1998,14(8)：36.
[121]聂淑琴,李泽琳,梁爱华,等.炮制对甘遂、牛膝、苦杏仁特殊毒性及药效的影响[J].中国中药杂志,1996,21(3)：153.
[122]李嗣英.甘遂对小鼠免疫功能的影响[J].中国药理通讯,1989,6(2)：10.
[123]Satoshi N, Susumu K, Chisei R.3-O-(2,3-Dimethylbutanoyl)-13-O-decanoylingenol from Euphorbia kansui Suppresses IgE-Mediated Mast Cell Activation[J].VoBiol PharmBull,2006,29(2):286-290.
[124]刘善庭,辛勤,李建美,等.生姜对呼吸平滑肌作用的实验研究[J].济宁医学院学报,1996,19(4)：26-27.
[125]张压西,陈友梅.针刺肺俞穴改善肺功能时效关系研究[J].中国针灸,1997,3(10)：581-582.
[126]胡志光等.针刺对支气管哮喘患者T淋巴细胞亚群和IL-4的影响[J].中国针灸,1999,19(2)：111.
[127]孙占玲,王伟.膻中穴埋线对哮喘豚鼠气道炎症的影响[J].浙江中医杂志,2007,7(42)：392-393
[128]刘幸平,许惠琴,狄留庆.定喘穴贴膏对过敏性哮喘豚鼠SOD、MDA、NO和NOS的影响[J].中医研究,2001,5(3)：9.
[129]Palmans E, Kips JC, Pauwels PA. Prolonged allergen exposure induces structural airway changes in sensitized rats[J]. Am J Respir Crit Care Med,2000,161(2):627-635.
[130]李惠民,赵顺英,江载芳.支气管上皮细胞在大鼠哮喘模型气道炎症和重塑中的作用[J].中国实用儿科杂志,2007,22(7)：526-530.
[131]李忠仁.实验针灸学[M].北京：中国中医药出版社,2003：325-326.
[132]刘金保,钟南山,李树浓,等.PPD对豚鼠实验性哮喘气道炎症的作用[J].免疫学杂志,2002,18(5)：350-352.
[133]黄艳,刘鑫,戴爱国,等.柴朴汤对卵蛋白诱导豚鼠哮喘的干预作用与对核因子-JB的影响[J].中医药导报,2007,13(6)：1-3.
[134]Schuster M, Tscherning T, Krug N, et al. Lymphocytes migrate from the blood into the bronchoalveolar lvage and lung parenchyma in the asthma model of the brown-norway rat[J]. Am J Respir Care Med,2000, 161(2):558-566.
[135]Sedgwiek J B. Vrtis R F, Jansen K J, et al. Peripheral blood Eosinophils from patients with allergic asthma contain increased intracellular eosinophil-derived neurotoxin[J]. J Allergy Clin Immunol,2004, 114(5):568-574.
[136]Southam DS, W idmerN, EllisR,et al. Increased eosinophil-lineage committed progenitors in the lung of allergen-challenged mice[J]. JAllergy Clin Immunol,2005,115(1):95-102.
[137]Ravensberg A J, Ricciardolo F L, van Schadewiik A, et al.Eotaxin-2 and eotaxin-3 expression is associated with Persistent eosinophilic bronchial inflammation in patients with asthma after allegen challenge[J]. J Allery Clin Immunol,2005,115(3):779-785.
[138]Stern M, Meagher L, Savil J, et al. Apoptosis in human eosinophils:Programmed cell death in the eosinophil leads to Phagocytosis by Macrophages and is modulated by IL-5[J]. J Immunol,1992,148(4): 3543-3549.
[139]Inman MD, Ellis R, Wattie J, et a.l.Allergen-induced increase in airway responsiveness, airway eosinophilia, and bone-marroweosinophil progenitors inmice[J].Am JRespirCellMolBiol,1999,21:473-479..
[140]Kitagaki K, Niwa S, Hoshiko K, et al. Augmentation of apoptosis in bronchal exuded rat eosinophils by cyclosporine A[J]. Biochem Bi-ophys Res Comnfun,1996,222(1):71-77.
[141]Letuve S, Druilhe A, Grandsaigne M, et al. Involvement of cas-pases and of mitochondria in Fas ligation-induced eosinophil apoptosis:modulation by interleukin-5 and interferon-gamma. J Leukoc Biol, 2001,70(4):767-775.
[142]Berro A I, Perry G A, Agrawal D K. Inereased expression and activation of CD30 induce apoptosis in human blood eosinophils. J Immunol,2004,173(5):2174-2183.
[143]Simon HU.Int Arch Allergy Immunl,1997,113(6):206-208.
[144]Chami M, Prandini A, Campanella M, et al. Bcl-2 and Bax exert opposing effects on Ca2+ signaling, which do not depend on their putative poreforming region[J]. J Biol Chem,2004,279(8):54-58.
[145]Youle R J, Strasser A. The Bcl-2 protein family:opposing activities that mediate cell death[J]. Nat Rev Mol Cell Biol,2008,9(1):47-59.
[146]Rathmell J C, Thompson C B. The central effectors of cell death in the immune system [J]. Annu Rev Immunol,1999,17(2):781-828.
[147]Voehringer D W, Meyn RE. Redox aspects of Bcl-2 function [J]. Antioxid Redox Signal,2000,22(2): 37-501.
[148]Dorscheid D R, Kimberly R. Apottosis of airway epithelial cells induced by corticosteroids[J]. Am J Respir Crit Care Med,2001,164(10):1939-1947.
[149]刘光伟,龚守良.细胞凋亡的线粒体调控机制与电离辐射[J].国外医学·放射医学核医学分册,2003：7(2)：90-93.
[150]Herr I, Debatin K. Cellular stress response and apoptosis in cancer therapy [J]. Blood,2001; 98(9): 2603-2604.
[151]Rudge E U, CutlerA J, Pritehard N R, et al. Interleukin 4 reduces expression of inhibitory receptors on B cells and abolishes CD22 and Fc gamma Rll-mediated B cell suppression[J].The Journal of ExP erimental Medieine,2009,195(8):1079-1085.
[152]Riifo V Y, Picthford S, Spina D. Cytokines in airway inflammation[J]. Int J Biochem Cell Biol,2000, 32(8):833-853.
[153]Hofstra C L, VanArk J, Hofiman G, et al. Different effeets of endogenous and esogenous interferon gamma on immunoglobulinE, cellular infiltration, and aiway respinsivenessin amurine model of allergy asthma[J]. Am J Respir Cell MoL Biol,1998,19(5):82-83.
[154]Finotto S, Neurath M F, Glickman J N, et al. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet[J]. Science,2002,295(3):336-338.
[155]Szabo S J, Kim S T, Costa G L, et al. A novel transcription factor, T-bet, directs Thl lineage commitment[J].Cell,2000,100(6):655-669.
[156]Assanasen P, Baroody F M, Naureckas E, et al.The nasal Passage of subjects with asthma has a decreased ability to warm and humidify inspired air[J]. Am J Respir Crit Care Med,2001,164:1640-1646.
[157]Nakamura Y, Ghaffar O, O livenstein R, et al. Gene expression of the GATA-3 transcription factors is increased in atopic asthma[J]. J Allergy C lin Immunol,1999,103(9):215-222.
[158]Zheng W, Flavell R A. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4+T cells[J]. Cell,1997,89(4):587-596.
[159]Dong L, Chen M, Zhang Q, et al. T-bet/GA-TA-3 ratio is a surrogate measure of Th1/Th2 cytokine profiles and may be novel targets for CpGODN treatment in asthma patients[J]. Chin Med J (Engl),2006, 119(16):1396-1399.
[160]刘春涛,王刚,罗凤鸣,等.支气管哮喘患者Th2细胞过度分化与转录因子T-bet和GATA-3的调控作用[J].中华结核和呼吸杂志,2004,6(27)：398-399.
© 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 |