川芎嗪对哮喘大鼠GATA-3及Th2型细胞因子表达的影响
摘要
【目的】研究腹腔注射川芎嗪对大鼠哮喘模型的防治作用及机制。
【方法】按常用方法制作大鼠哮喘模型并分为哮喘模型组(A组),川芎嗪治疗组(L组),地塞米松治疗对照组(D组)和正常对照组(N组)4组,每组8只。用酶联免疫吸附实验(ELISA)检测支气管肺泡灌洗液(BALF)中白介素-4(IL-4)和白介素-5(IL-5)的浓度。用HE染色的方法观察气道炎症变化。用免疫组化法研究肺组织GATA-3的表达。
【结果】(1)L组BALF中IL-4和IL-5明显低于A组的IL-4和IL-5,差异有显著性(P<0.01),与D组无显著差异(P>0.05)。(2)L组肺组织GATA-3阳性细胞的光密度值(OD值)明显低于A组OD值,差异有显著性(P<0.01),与D组无显著差异(P>0.05)。
【结论】腹腔注射川芎嗪可以抑制哮喘大鼠IL-4和IL-5的合成,其机制可能与其降低GATA-3在肺组织的表达,从而继发抑制Th2型免疫反应有关。
【Objective】To investigate the prevention and treatment effect of intraperritoneal ligustrazine on bronchial asthma in the SD rat asthma model and the relevant mechanism.
【Methods】The SD rat asthma model was made with classic method. All rats were divided into four groups, including asthma group (Group A, n=8), ligustrazine group (Group L, n=8), dexamethasone group (Group D, n=8), normal control group (Group N, n=8). The level of IL-4 and IL-5 in BALF were measured by ELISA. The airway inflammatory was observed with HE staining method. The expression of GATA-3 in pulmonary tissue was detected by means of immunohistochemicalstaining.
【Results】(1) The level of IL-4 and IL-5 in BALF in Group L were much lower than those in Group A (P<0.01), there was no statistical significant difference between Group L and Group D (P>0.05). (2) The optical density of GATA-3 positive cells in pulmonary tissue in Group L was much lower than that in Group A ( P<0.01), there was no statistical significant difference between Group L and Group D(P>0.05)。
【Conclusion】ligustrazine could lower the levels of IL-4 and IL-5 in the rat asthma model. The mechanism may be related to the action of ligustrazine to down-regulate GATA-3 expression in pulmonary tissue, resulting to suppression of Th2 reaction.
【方法】按常用方法制作大鼠哮喘模型并分为哮喘模型组(A组),川芎嗪治疗组(L组),地塞米松治疗对照组(D组)和正常对照组(N组)4组,每组8只。用酶联免疫吸附实验(ELISA)检测支气管肺泡灌洗液(BALF)中白介素-4(IL-4)和白介素-5(IL-5)的浓度。用HE染色的方法观察气道炎症变化。用免疫组化法研究肺组织GATA-3的表达。
【结果】(1)L组BALF中IL-4和IL-5明显低于A组的IL-4和IL-5,差异有显著性(P<0.01),与D组无显著差异(P>0.05)。(2)L组肺组织GATA-3阳性细胞的光密度值(OD值)明显低于A组OD值,差异有显著性(P<0.01),与D组无显著差异(P>0.05)。
【结论】腹腔注射川芎嗪可以抑制哮喘大鼠IL-4和IL-5的合成,其机制可能与其降低GATA-3在肺组织的表达,从而继发抑制Th2型免疫反应有关。
【Objective】To investigate the prevention and treatment effect of intraperritoneal ligustrazine on bronchial asthma in the SD rat asthma model and the relevant mechanism.
【Methods】The SD rat asthma model was made with classic method. All rats were divided into four groups, including asthma group (Group A, n=8), ligustrazine group (Group L, n=8), dexamethasone group (Group D, n=8), normal control group (Group N, n=8). The level of IL-4 and IL-5 in BALF were measured by ELISA. The airway inflammatory was observed with HE staining method. The expression of GATA-3 in pulmonary tissue was detected by means of immunohistochemicalstaining.
【Results】(1) The level of IL-4 and IL-5 in BALF in Group L were much lower than those in Group A (P<0.01), there was no statistical significant difference between Group L and Group D (P>0.05). (2) The optical density of GATA-3 positive cells in pulmonary tissue in Group L was much lower than that in Group A ( P<0.01), there was no statistical significant difference between Group L and Group D(P>0.05)。
【Conclusion】ligustrazine could lower the levels of IL-4 and IL-5 in the rat asthma model. The mechanism may be related to the action of ligustrazine to down-regulate GATA-3 expression in pulmonary tissue, resulting to suppression of Th2 reaction.
引文
1邓伟吾,郭雪君.肺部变应性疾病[M].上海:上海科学技术出版社,2000. 58.
2中华医学会第六次全国呼吸系学术会议纪要[J].中华结核和呼吸杂志,2001, 24 (1):8-11.
3 Lucey DR, Clerici M, Shearer GM. Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic,and inflammatory diseases [J]. Clin Microbiol Rev,1996,9(4): 532-562.
4 Barneses PJ, Lim S. Inhibitory cytokine in asthma [J]. Mol Med Toda, 1998, 4(10):452-458.
5 Wild JS, Sigounas A, Sur N, et al. IFN-γ-Inducing Factor (IL-18) Increases Allergic Sensitization , Serum IgE , Th2 Cytokines , and Airway Eosinophilia in a Mouse Model of Allergic Asthma [J]. J Immunol, 2000, 164 (5):2701-2710.
6 Nakamura Y, Ghaffar O, Olivenstein R, et al. Gene expression of the GATA-3 transcription factor is increased in atopic asthma [J]. J Allergy Clin Immunol, 1999, 103 (2):215-222.
7 Rifkin IR, Marshak-Rothstein A. T-bet: The Toll-bridge to classswitch recombination [J].Nature Immunology, 2003, 4:650-652.
8 Ray A, Cohn L. Th2 cells and GATA-3 in asthma: new insights into the regulation of airway inflammation [J]. J Clin Invest, 1999, 104(8):985-993.
9 Zheng W, Flavell RA.The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4+T cell [J]. Cell, 1997, 89(4):587.
10 Zhang DH , Yang L , Cohn LA , et al. Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3 [J]. Immunity, 1999, 11: 473-482.
11 Tamauchi H, Terashima M, Ito M, et al. Evidence of GATA-3-dependent Th2 commitment during the in vivo immune response [J]. Int Immunol, 2004, 16(1):179.
12 ROMAGNANI S.Cytokiness and chemoattractants in allergic inflammation [J]. Mol Immunol, 2002, 38(12-13):881-885.
13卢巍,梁标.白介素-4与支气管哮喘[J].国外医学(呼吸系统分册),2001, 21(3):126-129.
14卢巍,梁标.白介素-4与支气管哮喘[J].国外医学(呼吸系统分册),2001, 21(3):126-129.
15 Ferber IA, Lee HJ, Zonin F, et al. GATA-3 significantly downregulates IFN-γproduction from developing Th1 cell in addition to inducing IL-4 and IL-5 levels [J]. Clin Immunol, 1999, 91(2):134-144.
16林耀广.现代哮喘病学[M].北京:中国协和医科大学出版社,2004. 201.
17杨莉,王文建,李海浪,等.川芎嗪对哮喘大鼠气道壁胶原合成的影响[J].江苏医药,2003,29:818-819.
18吴迪华.川芎嗪治疗婴幼儿哮喘的疗效观察[J].中国中医急症,2000,9(2):63.
1邓伟吾,郭雪君.肺部变应性疾病[M].上海:上海科学技术出版社,2000. 58.
2中华医学会第六次全国呼吸系学术会议纪要[J].中华结核和呼吸杂志,2001, 24(1): 8-11.
3孔祥永,贾天明.Th2细胞和哮喘气道炎症[J].河南医学研究,2000, 9(3): 286-288.
4 Lukacs NW, Prosser DM, Wieowski M, et al. Requirement for the chemokine receptor ccR6 in allergic pulmonary inflammation [J]. J Exp Med, 2001, 194(4):551-555.
5 Shi HZ, Li CQ, Qin SM, et al. Effect of inhaled interleukin25 on number and activity of eoisonphils in circulation from asthmatics [J]. Clin Immunol, 1999, 91(2):163-169.
6 Das J, Chen CH, Yang L,et al.A critical role for NF-kappa B in GATA-3 expression and Th2 differentiation in allergic airway inflammation [J]. Nature Immunol, 2001, 2(1):45-50.
7 Labastie MC,Bories D,Chabret C ,et al. Structure and expression of the human GATA-3 gene [J]. Genomics, 1994, 21:1-6.
8 Ting CN ,Olson MC ,Barton KP ,et al. Transcription factor GATA-3 is required for development of the T-cell lineage [J].Nature, 1996, 384:474-478.
9 Lee HJ, Takemoto N, Kurata H, et al. GATA-3 induces T helper cell type2 (Th2) cytokine expression and chromatin remodeling in committed TH1 cells [J].J Exp Med, 2000, 192:105-115.
10 Zheng W, Flavell RA. The transcription factor GATA23 is necessary and sufficient for TH2 cytokine gene expression in CD4 T cells [J].Cell, 1997, 89:587-596.
11 Kishikawa H, Sun J, Choi A, et al. The cell type-specific expression of the murine IL213 gene is regulated by GATA-3 [J]. J Immunol, 2001, 167: 4414-4420.
12 Das J, Chen CH, Yang L, et al. A critical role for NF2kappa B in GATA-3 expression and TH2 differentiation in allergic airway inflammation [J]. Nat Immunol, 2001, 2:45-50.
13 Nakamura Y, Ghaffar O, Olivenstein R, et al. Gene expression of the GATA-3 transcription factor is increased in atopic asthma [J]. J Allergy Clin Immunol, 1999, 103:215-222.
14 Caramori G, Lim S, Ito K, et al. Expression of GATA family of transcription factors inT-cells. monocytes and bronchial biopsies [J]. Eur Respir J, 2001, 18:466-473.
15 Christodoulopoulos P, Cameron L, Nakamura Y, et al. Th2 cytokine-associated transcription factors in atopic and nonatopic asthma: evidence for differential signal transducer and activator of transcription 6 expression [J]. J Allergy Clin Immunol, 2001, 107:586-591.
16 Justice J P ,Borchers MT ,Lee J ,et al. Ragweed2induced expression of GATA-3, IL-4, and IL-5 by eosinophils in the lungs of allergic C57BL/6J mice [J].Am J Physiol Lung Cell Mol Physiol, 2002, 282:L302-309.
17 Zhang DH, Yang L, Cohn LA, et al. Inhibition of allergic inflammation in a murine model of asthma by expression of a dominantnegative mutant of GATA-3 [J]. Immunity, 1999, 11:473-482.
18 Finotto S, Sanctis GT, Lehr HA, et al. Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression [J]. J Exp Med, 2001, 193:1247-1260.
19 Szabo SJ, Kim ST, Costa GL, et al.[J]. Cell, 2000, 100(6):655-669.
20 Mullen AC, Hutchins AS, Villarino AV, et al. Cell cycle controlling the silencing and functioning of mammalian activators [J].Cur Biol, 2001, 11 (21):1695-1699.
21刘杰,魏海明,田志刚,等. Th1/Th2相关细胞因子基因检测方法的建立[J].中国免疫学杂志,1999, 15(8):550-552.
22 Mullen AC, High FA, Hutchins AS, et al. Role of T-bet in Commitment of Th1 Cells Before IL-12-Dependent Selection [J].Science, 2001, 292(5523): 1907-1910.
23魏海明,田志刚. Th1/Th2 :转录因子的作用[J].上海免疫学杂志, 2001, 21(6): 379-381.
24 Szabo SJ, Sullivan BM, Stemmann C, et al. Distinct Effects of T-bet in Th1 Lineage Commitment and IFN-γProduction in CD4 and CD8 T Cells [J]. Science, 2002, 295(5553):338-342.
25 Finotto S, Neurath MF, Glickman JN, et al.[J] .Science, 2002, 295:336-338.
26 Lighvani AA, Frucht M, Jankovic D, et al.[J] .Proc Natl Acad Sci USA, 2001, 98:15137-15142.
27 Barat FJ, Cua DJ, Boonstra A, et al.[J].J Exp Med, 2002, 195:603-616.
28 Finotto S, Markus F, Neurath MF, et al.[J].Science, 2002, 295:336-338.
1郭顺根,牛建昭,贲长恩,等.3H-川芎嗪在动物体内分布的放射自显影研究[J].中国医药学报, 1989, 4(3):17-21,80.
2黄志力,桂常青,孙瑞元.盐酸川芎嗪在大鼠体内的分布[J].中国药理学通报, 1994, 10(4):297-299.
3刘晓勤,楼雅卿,陈清棠.正常人及缺血性脑血管病病人的盐酸川芎嗪临床药代动力学研究[J].中国临床药理学杂志,1991, 7(1):32-36.
4江骥,姜国辉,叶云鹏,等.川芎嗪的体内代谢[J].中国医学科学院学报, 1993, 15(2):79-81.
5赵永辰,陈信义.川芎嗪临床应用研究[J].中国医药学报,2002, 17(1):53-56.
6戴令娟,侯杰,黄妹,等.川芎嗪治疗肺纤维化机制的探讨[J].医师进修杂志,1999, 22(11):24-25.
7张飞,周汝元.川芎嗪对先心病肺动脉高压影响作用的研究[J].安徽医科大学学报, 2005, 40(3):241-244.
8王树山,刘福泽,孙志霞.静滴川芎嗪治疗哮喘持续状态50例[J].实用儿科临床杂志,1993, 8(4): 254-255.
9李静美,黄庆山,任义先.川芎嗪超声雾化吸入治疗小儿哮喘性支气管炎[J].中国中医急症,1996, 5(2):61.
10聂国明.川芎嗪佐治支气管哮喘疗效观察[J].华南国防医学杂志, 2003, 17(1): 39-40.
11谢浩,孙胜辉.阿奇霉素联合川芎嗪治疗糖皮质激素抵抗型哮喘疗效观察[J].现代中西医结合杂志, 2004, 13(8):987-988.
12郭一兵,陈金安.川芎嗪合普米克治疗儿童哮喘30例临床观察[J].中医儿科杂志, 2006, 2(5):30-31.
13张瑞祥,张劲农,陶晓南,等.川芎嗪对几种致喘介质所致离体豚鼠气管条收缩作用的影响[J].中国药理学通报, 1990, 6(3):187.
14王良兴,邢玲玲,陈可贤,等.川芎嗪对组胺和乙酰胆碱所致离体豚鼠气管条收缩作用的影响[J].温州医学院学报,1995, 3:158-159.
15李荣,张珍祥.川芎嗪在豚鼠离体气管螺旋条中的作用[J].中国病理生理杂志, 2002, 18(5):521.
16杨燕秋,黎锐发,许继德,等.川芎嗪注射液对离体豚鼠气管平滑肌作用机制探讨[J].中国临床药理学与治疗学, 2004, 9(5):558-560.
17倪健,董竞成.三种中药药效成分抗支气管哮喘变应性炎症的实验研究[J].中国实验方剂学杂志, 2004, 10(4):49-51.
18于化鹏,李平升,府军.过敏性哮喘豚鼠血小板激活因子的变化及川芎嗪的影响[J].中国病理生理杂志, 1995, 11(3):317-320.
19刘先胜,徐永健,张珍祥,等.川芎嗪对人外周血淋巴细胞蛋白激酶C通道的影响[J].中国病理生理杂志, 2003, 19(4):507-510.
20 Kenyon NJ, Ward RW, McGrew G, et al. TGF-beta1 causes airway fibrosis and increased collagenⅠandⅢmRNA in mice [J].Thorax, 2003, 58:772-777.
21杨莉,王文建,李海浪,等.川芎嗪对哮喘大鼠气道壁胶原合成的影响[J].江苏医药, 2003, 29(11):818-819.
22王文建,杨莉,李海浪,等.川芎嗪对哮喘大鼠气道壁平滑肌增殖及TGF-β1表达的影响[J].东南大学学报(医学版),2003, 22(6):387-390.
23 BORLAND G, ROSSJ A, GUY K. Forms and functions of CD44 [J].Immunology, 1998, 93:139-148.
24 ROTHENBERGM E. CD44: a sticky target for asthma [J]. J Clin Invest, 2003, 111:1460-1462.
25 WUTHRICH R P. The proinflammatory role of hyaluronan CD44 interactions in renal injury [J]. Nephrol Dial Transplant, 1999, 14: 2554-2556.
26李羚,杨莉,唐珩,等.川芎嗪对哮喘大鼠肺组织CD44干预机制的实验研究[J].现代医学2005, 33(3):174-176.
27 SJOSWARD K N, UPPUGUNDUR I S, SCHMEKEL B. Decreased serum levels of P-selectin and eosinophil cationic protein in patients with mild asthma after inhaled salbutamol [J].Respiration, 2004, 71(3):241-245.
28 WAGNER D D. P-selectin chases a butterfly [J]. Clin Invest, 1995, 95(5):1955-1956.
29于化鹏,任锦云,王富强,等. P选择素在速激肽类致气道高反应性中的作用[J].中华内科杂志, 1999, 38(4):228-230.
30唐珩,杨莉,李羚,等.川芎嗪对哮喘大鼠血清P选择素表达的影响[J].现代医学, 2006, 34(3):174-176.
31 ROMAGNANI S. Cytokiness and chemoattractants in allergic inflammation [J].Mol Immunol, 2002, 38(12-13):881-885.
32金蕊,杨莉,陈径,等.川芎嗪对哮喘大鼠Th2型细胞因子作用的研究[J].现代医学, 2006, 34(5):327-329.
33 BARNES P J. Nuclear factor-kappa B [J]. Int J Biochem Cell Biol, 1997, 29:867-870.
34 HARTL A, KRISHNAN V L, ADCOCK I M, et al. Activation and localization of transcription factor, nuclear factor- kappa B, in asthma [J]. Am J Respir Crit Care Med, 1998, 158 (5 Pt 1):1585-1592.
35陈径,杨莉,金蕊,等.川芎嗪对哮喘大鼠NF-κB表达及气道炎症的影响[J].现代医学,2005, 33(6):351-353.
36 Finotto S, De Sanctis GT, Lehr HA, et al.Treatment of allergic airway inflammation and hyperresponsiveness by antisence-induced local blockade of GATA-3 expression [J].J Exp Med, 2001, 193:1247-1260.
37吉宁飞,卞涛,符晓苏,等.川芎嗪对支气管哮喘大鼠肺组织转录因子GATA-3表达的影响[J].中华结核和呼吸杂志, 2006, 29(12):852-853.
38 Rifkin IR, Marshak-Rothstein A. T-bet: The Toll-bridge to classswitch recombination [J].Nature Immunology, 2003, 4:650-652.
39 Szabo SJ, Kim ST, Costa GL, et al. A novel transcription factor, T-bet, directs Th1 lineage commitment [J].Cell, 2000, 100:655-669.
40肖伟,郑春燕,孙继平,等.肺癌患者Th1/Th2状态及川芎嗪的调节作用[J].上海免疫学杂志, 2001, 21(4):242-245.
41杨莉,陈径,王文建,等.川芎嗪对哮喘大鼠Th1/Th2型细胞因子水平的影响[J].江苏医药, 2004, 30(11):822-823.
2中华医学会第六次全国呼吸系学术会议纪要[J].中华结核和呼吸杂志,2001, 24 (1):8-11.
3 Lucey DR, Clerici M, Shearer GM. Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic,and inflammatory diseases [J]. Clin Microbiol Rev,1996,9(4): 532-562.
4 Barneses PJ, Lim S. Inhibitory cytokine in asthma [J]. Mol Med Toda, 1998, 4(10):452-458.
5 Wild JS, Sigounas A, Sur N, et al. IFN-γ-Inducing Factor (IL-18) Increases Allergic Sensitization , Serum IgE , Th2 Cytokines , and Airway Eosinophilia in a Mouse Model of Allergic Asthma [J]. J Immunol, 2000, 164 (5):2701-2710.
6 Nakamura Y, Ghaffar O, Olivenstein R, et al. Gene expression of the GATA-3 transcription factor is increased in atopic asthma [J]. J Allergy Clin Immunol, 1999, 103 (2):215-222.
7 Rifkin IR, Marshak-Rothstein A. T-bet: The Toll-bridge to classswitch recombination [J].Nature Immunology, 2003, 4:650-652.
8 Ray A, Cohn L. Th2 cells and GATA-3 in asthma: new insights into the regulation of airway inflammation [J]. J Clin Invest, 1999, 104(8):985-993.
9 Zheng W, Flavell RA.The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4+T cell [J]. Cell, 1997, 89(4):587.
10 Zhang DH , Yang L , Cohn LA , et al. Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3 [J]. Immunity, 1999, 11: 473-482.
11 Tamauchi H, Terashima M, Ito M, et al. Evidence of GATA-3-dependent Th2 commitment during the in vivo immune response [J]. Int Immunol, 2004, 16(1):179.
12 ROMAGNANI S.Cytokiness and chemoattractants in allergic inflammation [J]. Mol Immunol, 2002, 38(12-13):881-885.
13卢巍,梁标.白介素-4与支气管哮喘[J].国外医学(呼吸系统分册),2001, 21(3):126-129.
14卢巍,梁标.白介素-4与支气管哮喘[J].国外医学(呼吸系统分册),2001, 21(3):126-129.
15 Ferber IA, Lee HJ, Zonin F, et al. GATA-3 significantly downregulates IFN-γproduction from developing Th1 cell in addition to inducing IL-4 and IL-5 levels [J]. Clin Immunol, 1999, 91(2):134-144.
16林耀广.现代哮喘病学[M].北京:中国协和医科大学出版社,2004. 201.
17杨莉,王文建,李海浪,等.川芎嗪对哮喘大鼠气道壁胶原合成的影响[J].江苏医药,2003,29:818-819.
18吴迪华.川芎嗪治疗婴幼儿哮喘的疗效观察[J].中国中医急症,2000,9(2):63.
1邓伟吾,郭雪君.肺部变应性疾病[M].上海:上海科学技术出版社,2000. 58.
2中华医学会第六次全国呼吸系学术会议纪要[J].中华结核和呼吸杂志,2001, 24(1): 8-11.
3孔祥永,贾天明.Th2细胞和哮喘气道炎症[J].河南医学研究,2000, 9(3): 286-288.
4 Lukacs NW, Prosser DM, Wieowski M, et al. Requirement for the chemokine receptor ccR6 in allergic pulmonary inflammation [J]. J Exp Med, 2001, 194(4):551-555.
5 Shi HZ, Li CQ, Qin SM, et al. Effect of inhaled interleukin25 on number and activity of eoisonphils in circulation from asthmatics [J]. Clin Immunol, 1999, 91(2):163-169.
6 Das J, Chen CH, Yang L,et al.A critical role for NF-kappa B in GATA-3 expression and Th2 differentiation in allergic airway inflammation [J]. Nature Immunol, 2001, 2(1):45-50.
7 Labastie MC,Bories D,Chabret C ,et al. Structure and expression of the human GATA-3 gene [J]. Genomics, 1994, 21:1-6.
8 Ting CN ,Olson MC ,Barton KP ,et al. Transcription factor GATA-3 is required for development of the T-cell lineage [J].Nature, 1996, 384:474-478.
9 Lee HJ, Takemoto N, Kurata H, et al. GATA-3 induces T helper cell type2 (Th2) cytokine expression and chromatin remodeling in committed TH1 cells [J].J Exp Med, 2000, 192:105-115.
10 Zheng W, Flavell RA. The transcription factor GATA23 is necessary and sufficient for TH2 cytokine gene expression in CD4 T cells [J].Cell, 1997, 89:587-596.
11 Kishikawa H, Sun J, Choi A, et al. The cell type-specific expression of the murine IL213 gene is regulated by GATA-3 [J]. J Immunol, 2001, 167: 4414-4420.
12 Das J, Chen CH, Yang L, et al. A critical role for NF2kappa B in GATA-3 expression and TH2 differentiation in allergic airway inflammation [J]. Nat Immunol, 2001, 2:45-50.
13 Nakamura Y, Ghaffar O, Olivenstein R, et al. Gene expression of the GATA-3 transcription factor is increased in atopic asthma [J]. J Allergy Clin Immunol, 1999, 103:215-222.
14 Caramori G, Lim S, Ito K, et al. Expression of GATA family of transcription factors inT-cells. monocytes and bronchial biopsies [J]. Eur Respir J, 2001, 18:466-473.
15 Christodoulopoulos P, Cameron L, Nakamura Y, et al. Th2 cytokine-associated transcription factors in atopic and nonatopic asthma: evidence for differential signal transducer and activator of transcription 6 expression [J]. J Allergy Clin Immunol, 2001, 107:586-591.
16 Justice J P ,Borchers MT ,Lee J ,et al. Ragweed2induced expression of GATA-3, IL-4, and IL-5 by eosinophils in the lungs of allergic C57BL/6J mice [J].Am J Physiol Lung Cell Mol Physiol, 2002, 282:L302-309.
17 Zhang DH, Yang L, Cohn LA, et al. Inhibition of allergic inflammation in a murine model of asthma by expression of a dominantnegative mutant of GATA-3 [J]. Immunity, 1999, 11:473-482.
18 Finotto S, Sanctis GT, Lehr HA, et al. Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression [J]. J Exp Med, 2001, 193:1247-1260.
19 Szabo SJ, Kim ST, Costa GL, et al.[J]. Cell, 2000, 100(6):655-669.
20 Mullen AC, Hutchins AS, Villarino AV, et al. Cell cycle controlling the silencing and functioning of mammalian activators [J].Cur Biol, 2001, 11 (21):1695-1699.
21刘杰,魏海明,田志刚,等. Th1/Th2相关细胞因子基因检测方法的建立[J].中国免疫学杂志,1999, 15(8):550-552.
22 Mullen AC, High FA, Hutchins AS, et al. Role of T-bet in Commitment of Th1 Cells Before IL-12-Dependent Selection [J].Science, 2001, 292(5523): 1907-1910.
23魏海明,田志刚. Th1/Th2 :转录因子的作用[J].上海免疫学杂志, 2001, 21(6): 379-381.
24 Szabo SJ, Sullivan BM, Stemmann C, et al. Distinct Effects of T-bet in Th1 Lineage Commitment and IFN-γProduction in CD4 and CD8 T Cells [J]. Science, 2002, 295(5553):338-342.
25 Finotto S, Neurath MF, Glickman JN, et al.[J] .Science, 2002, 295:336-338.
26 Lighvani AA, Frucht M, Jankovic D, et al.[J] .Proc Natl Acad Sci USA, 2001, 98:15137-15142.
27 Barat FJ, Cua DJ, Boonstra A, et al.[J].J Exp Med, 2002, 195:603-616.
28 Finotto S, Markus F, Neurath MF, et al.[J].Science, 2002, 295:336-338.
1郭顺根,牛建昭,贲长恩,等.3H-川芎嗪在动物体内分布的放射自显影研究[J].中国医药学报, 1989, 4(3):17-21,80.
2黄志力,桂常青,孙瑞元.盐酸川芎嗪在大鼠体内的分布[J].中国药理学通报, 1994, 10(4):297-299.
3刘晓勤,楼雅卿,陈清棠.正常人及缺血性脑血管病病人的盐酸川芎嗪临床药代动力学研究[J].中国临床药理学杂志,1991, 7(1):32-36.
4江骥,姜国辉,叶云鹏,等.川芎嗪的体内代谢[J].中国医学科学院学报, 1993, 15(2):79-81.
5赵永辰,陈信义.川芎嗪临床应用研究[J].中国医药学报,2002, 17(1):53-56.
6戴令娟,侯杰,黄妹,等.川芎嗪治疗肺纤维化机制的探讨[J].医师进修杂志,1999, 22(11):24-25.
7张飞,周汝元.川芎嗪对先心病肺动脉高压影响作用的研究[J].安徽医科大学学报, 2005, 40(3):241-244.
8王树山,刘福泽,孙志霞.静滴川芎嗪治疗哮喘持续状态50例[J].实用儿科临床杂志,1993, 8(4): 254-255.
9李静美,黄庆山,任义先.川芎嗪超声雾化吸入治疗小儿哮喘性支气管炎[J].中国中医急症,1996, 5(2):61.
10聂国明.川芎嗪佐治支气管哮喘疗效观察[J].华南国防医学杂志, 2003, 17(1): 39-40.
11谢浩,孙胜辉.阿奇霉素联合川芎嗪治疗糖皮质激素抵抗型哮喘疗效观察[J].现代中西医结合杂志, 2004, 13(8):987-988.
12郭一兵,陈金安.川芎嗪合普米克治疗儿童哮喘30例临床观察[J].中医儿科杂志, 2006, 2(5):30-31.
13张瑞祥,张劲农,陶晓南,等.川芎嗪对几种致喘介质所致离体豚鼠气管条收缩作用的影响[J].中国药理学通报, 1990, 6(3):187.
14王良兴,邢玲玲,陈可贤,等.川芎嗪对组胺和乙酰胆碱所致离体豚鼠气管条收缩作用的影响[J].温州医学院学报,1995, 3:158-159.
15李荣,张珍祥.川芎嗪在豚鼠离体气管螺旋条中的作用[J].中国病理生理杂志, 2002, 18(5):521.
16杨燕秋,黎锐发,许继德,等.川芎嗪注射液对离体豚鼠气管平滑肌作用机制探讨[J].中国临床药理学与治疗学, 2004, 9(5):558-560.
17倪健,董竞成.三种中药药效成分抗支气管哮喘变应性炎症的实验研究[J].中国实验方剂学杂志, 2004, 10(4):49-51.
18于化鹏,李平升,府军.过敏性哮喘豚鼠血小板激活因子的变化及川芎嗪的影响[J].中国病理生理杂志, 1995, 11(3):317-320.
19刘先胜,徐永健,张珍祥,等.川芎嗪对人外周血淋巴细胞蛋白激酶C通道的影响[J].中国病理生理杂志, 2003, 19(4):507-510.
20 Kenyon NJ, Ward RW, McGrew G, et al. TGF-beta1 causes airway fibrosis and increased collagenⅠandⅢmRNA in mice [J].Thorax, 2003, 58:772-777.
21杨莉,王文建,李海浪,等.川芎嗪对哮喘大鼠气道壁胶原合成的影响[J].江苏医药, 2003, 29(11):818-819.
22王文建,杨莉,李海浪,等.川芎嗪对哮喘大鼠气道壁平滑肌增殖及TGF-β1表达的影响[J].东南大学学报(医学版),2003, 22(6):387-390.
23 BORLAND G, ROSSJ A, GUY K. Forms and functions of CD44 [J].Immunology, 1998, 93:139-148.
24 ROTHENBERGM E. CD44: a sticky target for asthma [J]. J Clin Invest, 2003, 111:1460-1462.
25 WUTHRICH R P. The proinflammatory role of hyaluronan CD44 interactions in renal injury [J]. Nephrol Dial Transplant, 1999, 14: 2554-2556.
26李羚,杨莉,唐珩,等.川芎嗪对哮喘大鼠肺组织CD44干预机制的实验研究[J].现代医学2005, 33(3):174-176.
27 SJOSWARD K N, UPPUGUNDUR I S, SCHMEKEL B. Decreased serum levels of P-selectin and eosinophil cationic protein in patients with mild asthma after inhaled salbutamol [J].Respiration, 2004, 71(3):241-245.
28 WAGNER D D. P-selectin chases a butterfly [J]. Clin Invest, 1995, 95(5):1955-1956.
29于化鹏,任锦云,王富强,等. P选择素在速激肽类致气道高反应性中的作用[J].中华内科杂志, 1999, 38(4):228-230.
30唐珩,杨莉,李羚,等.川芎嗪对哮喘大鼠血清P选择素表达的影响[J].现代医学, 2006, 34(3):174-176.
31 ROMAGNANI S. Cytokiness and chemoattractants in allergic inflammation [J].Mol Immunol, 2002, 38(12-13):881-885.
32金蕊,杨莉,陈径,等.川芎嗪对哮喘大鼠Th2型细胞因子作用的研究[J].现代医学, 2006, 34(5):327-329.
33 BARNES P J. Nuclear factor-kappa B [J]. Int J Biochem Cell Biol, 1997, 29:867-870.
34 HARTL A, KRISHNAN V L, ADCOCK I M, et al. Activation and localization of transcription factor, nuclear factor- kappa B, in asthma [J]. Am J Respir Crit Care Med, 1998, 158 (5 Pt 1):1585-1592.
35陈径,杨莉,金蕊,等.川芎嗪对哮喘大鼠NF-κB表达及气道炎症的影响[J].现代医学,2005, 33(6):351-353.
36 Finotto S, De Sanctis GT, Lehr HA, et al.Treatment of allergic airway inflammation and hyperresponsiveness by antisence-induced local blockade of GATA-3 expression [J].J Exp Med, 2001, 193:1247-1260.
37吉宁飞,卞涛,符晓苏,等.川芎嗪对支气管哮喘大鼠肺组织转录因子GATA-3表达的影响[J].中华结核和呼吸杂志, 2006, 29(12):852-853.
38 Rifkin IR, Marshak-Rothstein A. T-bet: The Toll-bridge to classswitch recombination [J].Nature Immunology, 2003, 4:650-652.
39 Szabo SJ, Kim ST, Costa GL, et al. A novel transcription factor, T-bet, directs Th1 lineage commitment [J].Cell, 2000, 100:655-669.
40肖伟,郑春燕,孙继平,等.肺癌患者Th1/Th2状态及川芎嗪的调节作用[J].上海免疫学杂志, 2001, 21(4):242-245.
41杨莉,陈径,王文建,等.川芎嗪对哮喘大鼠Th1/Th2型细胞因子水平的影响[J].江苏医药, 2004, 30(11):822-823.