苈桃抗纤方对肺泡Ⅱ型上皮细胞转化的影响及作用机制
|
摘要
研究背景:肺纤维化(pulmonary fibrosis,PF)是以运动性呼吸困难进行性加重,以喘息、气短、干咳、喘憋为临床表现,以限制性通气功能障碍、低氧血症、慢性进行性弥漫性肺间质纤维化为特点的肺间质性疾病。肺纤维化既是多种肺疾病、多种系统性疾病的共同结局,又有无原发疾病的特发性肺间质纤维化。
近年来,随着细胞和分子生物学等生命科学理论研究,多种研究手段的应用,从器官、组织、细胞、分子的不同层次,对肺纤维化的发生、诊断、防治的研究不断深入,取得极大的进展。
研究表明,肺纤维化是由早期组织损伤、炎症变化发展而来,而肺部受感染或损伤后,肺泡上皮细胞和是最早受到损伤的靶细胞。由于肺泡表面约93-97%的肺泡Ⅰ型上皮细胞为终末细胞,不能进行分裂增殖,故具有增殖分化能力的肺泡Ⅱ型上皮细胞(Alveolar typeⅡcell,ATⅡ)是参与组织损伤修复的主要细胞,所以,最初肺损伤后发生于组织修复时的肺泡Ⅱ型上皮细胞向间质细胞转化(epithelial to mesenchymaltransition,EMT)在肺纤维化发生发展过程中发挥着极其重要的作用。
近年来随着对肺纤维化的发病机理的深入研究,无论中、西医均在治疗上取得相当进展。导师在长期的临床实践中,依照经验创立苈桃抗纤方,对肺间质纤维化患者进行雾化治疗,取得了一定的疗效。为了提高它的可信度和可重复性,为临床实践提供更好生命科学理论基础,在本实验中,我们主要研究苈桃抗纤方对肺泡Ⅱ型上皮细胞向问质细胞转化、EMT转化率以及对肺泡Ⅱ型上皮细胞转化过程中相关细胞转导通路的影响,在细胞及分子水平上探讨苈桃抗纤方抗肺纤维化的生物学基础。
目的:由于肺泡Ⅱ型上皮细胞向间质细胞转化(EMT)是发生肺纤维化的重要因素,故在本次实验中,我们应用转化生长因子(transforminggrowth factor TGF-β1)诱导人肺上皮细胞系(A549)EMT发生,观察TGF-β1对A549增殖及形态变化的影响,研究苈桃抗纤方雾滴干预后对肺泡Ⅱ型上皮细胞向间质细胞转化的影响,从基于雾化中药制剂影响EMT发生的角度,初步探讨苈桃抗纤方防治肺纤维化的生物学基础。
方法:使用不同浓度苈桃抗纤方体外干预A549细胞。免疫组化法检测细胞内TGF-β1的相对含量;通过TGF-β1体外诱导细胞EMT的发生,ELISA法检测细胞角蛋白(cytokeratin)及波形蛋白(Vimentin)表达,计算细胞EMT转化率;Real-time PCR法检测苈桃抗纤方对细胞内Ⅰ型胶原及Ⅲ型胶原mRNA表达的影响;Western Blot检测细胞磷酸化(phosphorylation)Erk1/2的表达。
结果:不同浓度苈桃抗纤方体外作用A549细胞48h后,胞内TGF-β1的定量表达,相较正常对照组明显减少(40.35±1.65,37.84±0.95,37.45±0.78 VS 45.13±2.01),(P<0.01)具有显著差异性。TGF-β1体外诱导A549细胞EMT发生后,ELISA检测细胞cytokeratin和vimentin表达显示,相较正常对照组,vimentin阳性表达明显增强,而cytokeratin阳性表达相对减弱;RT-PCR检测表明,A549细胞内Ⅰ型胶原及Ⅲ型胶原mRNA表达显著增强。经不同浓度苈桃抗纤方体外作用诱导EMT成功的A549细胞48h后,与模型组相比,vimentin阳性表达出现不同程度的减弱,而cytokeratin阳性表达则出现不同程度增强;Ⅰ型胶原及Ⅲ型胶原mRNA表达均出现不同程度下调;phosphorylation Erk1/2的表达减弱。
结论:苈桃抗纤方可以降低TGF-β1诱导的A549细胞EMT转化率,阻断肺泡Ⅱ型上皮细胞向间质细胞转化,减少肺成纤维细胞的产生,从而抑制肺纤维化的发生,达到抗肺纤维化的作用。其可能机制是通过降低细胞内转化生长因子(transforming growth factor TGF-β1)的释放,干预Ⅰ型及Ⅲ型胶原mRNA表达,影响细胞磷酸化Erk1/2的表达。
Objective:Pulmonary fibrosis results from infection,drugs, chemicals,organic or inorganic dust,and other autoimmune diseases,that stimulate alveolar damage.It is a leading cause of Chronic obstructive pulmonary disease、Idiopathic pulmonary fibrosis and other serious lung diseases.As the alveolar epithelial typeⅡcells to mesenchymal cell transformation(EMT) is an important factors of pulmonary fibrosis,so we adopted A549 cells in this experiment and used transforming growth factor induced EMT to occur in A549 cells to study the effect of Li Tao Kang Xian Fang droplet in EMT.Real-time PCR,Western-blot and ELISA was introduced to define the biology basic of Li Tao Kang Xian Fang droplet playing a anti- fibrosis role by controling EMT.
Methods:Different concentrations of Li Tao Kang Xian Fang was used to intervene A549 cells in vitro.ELISA were used to show the retative contents of the TGF-β1 in A549 cells.We used TGF-β1 to induce the occurrence of EMT.The collagenⅠand collagenⅢmRNA level was monitored by real-time PCR,the protein level of phosphorylation Erk1/2 were examined by western blot analysis. Cell apoptosis and cell cycle distribution were determined by flow cytometry.The protein level of phosphorylation Erk1/2 were examined by western blot analysis.
Results:Our data showed that contents of the TGF-β1 ruduced after 24h intervention of different concentrations of Li Tao Kang Xian Fang.In TGF-β1-induced cells,vimentin espression have a sharp increase but cytokeratina espression have a relative reduction.The level of collagenⅠandⅢshow Significantly higher.By intervening of different concentrations of Li Tao Kang Xian Fang,vimentin espression was significantly lower,yet cytokeratina espression was significantly higher than that in the model group.Meantime,It bring a obvious reduction in espression of collagenⅠ、Ⅲand phosphorylation Erk1/2.
Conclusion:Li Tao Kang Xian Fang can drop the EMT rates of TGF-β1 -induced A549 cells,thereby ruduce ACEⅡcells to epithelial cells.It lead to a reduction of lung fibroblast production,to inhibit the occurrence of pulmonary fibrosis,so as to achieve an anti- fibrosis role.The possible mechanism maybe by reducing the transforming growth factor(TGF-β) releasion,interveningⅠandⅢcollagen mRNA expression,and affecting cell phosphorylation Erk1/ 2 expression.
近年来,随着细胞和分子生物学等生命科学理论研究,多种研究手段的应用,从器官、组织、细胞、分子的不同层次,对肺纤维化的发生、诊断、防治的研究不断深入,取得极大的进展。
研究表明,肺纤维化是由早期组织损伤、炎症变化发展而来,而肺部受感染或损伤后,肺泡上皮细胞和是最早受到损伤的靶细胞。由于肺泡表面约93-97%的肺泡Ⅰ型上皮细胞为终末细胞,不能进行分裂增殖,故具有增殖分化能力的肺泡Ⅱ型上皮细胞(Alveolar typeⅡcell,ATⅡ)是参与组织损伤修复的主要细胞,所以,最初肺损伤后发生于组织修复时的肺泡Ⅱ型上皮细胞向间质细胞转化(epithelial to mesenchymaltransition,EMT)在肺纤维化发生发展过程中发挥着极其重要的作用。
近年来随着对肺纤维化的发病机理的深入研究,无论中、西医均在治疗上取得相当进展。导师在长期的临床实践中,依照经验创立苈桃抗纤方,对肺间质纤维化患者进行雾化治疗,取得了一定的疗效。为了提高它的可信度和可重复性,为临床实践提供更好生命科学理论基础,在本实验中,我们主要研究苈桃抗纤方对肺泡Ⅱ型上皮细胞向问质细胞转化、EMT转化率以及对肺泡Ⅱ型上皮细胞转化过程中相关细胞转导通路的影响,在细胞及分子水平上探讨苈桃抗纤方抗肺纤维化的生物学基础。
目的:由于肺泡Ⅱ型上皮细胞向间质细胞转化(EMT)是发生肺纤维化的重要因素,故在本次实验中,我们应用转化生长因子(transforminggrowth factor TGF-β1)诱导人肺上皮细胞系(A549)EMT发生,观察TGF-β1对A549增殖及形态变化的影响,研究苈桃抗纤方雾滴干预后对肺泡Ⅱ型上皮细胞向间质细胞转化的影响,从基于雾化中药制剂影响EMT发生的角度,初步探讨苈桃抗纤方防治肺纤维化的生物学基础。
方法:使用不同浓度苈桃抗纤方体外干预A549细胞。免疫组化法检测细胞内TGF-β1的相对含量;通过TGF-β1体外诱导细胞EMT的发生,ELISA法检测细胞角蛋白(cytokeratin)及波形蛋白(Vimentin)表达,计算细胞EMT转化率;Real-time PCR法检测苈桃抗纤方对细胞内Ⅰ型胶原及Ⅲ型胶原mRNA表达的影响;Western Blot检测细胞磷酸化(phosphorylation)Erk1/2的表达。
结果:不同浓度苈桃抗纤方体外作用A549细胞48h后,胞内TGF-β1的定量表达,相较正常对照组明显减少(40.35±1.65,37.84±0.95,37.45±0.78 VS 45.13±2.01),(P<0.01)具有显著差异性。TGF-β1体外诱导A549细胞EMT发生后,ELISA检测细胞cytokeratin和vimentin表达显示,相较正常对照组,vimentin阳性表达明显增强,而cytokeratin阳性表达相对减弱;RT-PCR检测表明,A549细胞内Ⅰ型胶原及Ⅲ型胶原mRNA表达显著增强。经不同浓度苈桃抗纤方体外作用诱导EMT成功的A549细胞48h后,与模型组相比,vimentin阳性表达出现不同程度的减弱,而cytokeratin阳性表达则出现不同程度增强;Ⅰ型胶原及Ⅲ型胶原mRNA表达均出现不同程度下调;phosphorylation Erk1/2的表达减弱。
结论:苈桃抗纤方可以降低TGF-β1诱导的A549细胞EMT转化率,阻断肺泡Ⅱ型上皮细胞向间质细胞转化,减少肺成纤维细胞的产生,从而抑制肺纤维化的发生,达到抗肺纤维化的作用。其可能机制是通过降低细胞内转化生长因子(transforming growth factor TGF-β1)的释放,干预Ⅰ型及Ⅲ型胶原mRNA表达,影响细胞磷酸化Erk1/2的表达。
Objective:Pulmonary fibrosis results from infection,drugs, chemicals,organic or inorganic dust,and other autoimmune diseases,that stimulate alveolar damage.It is a leading cause of Chronic obstructive pulmonary disease、Idiopathic pulmonary fibrosis and other serious lung diseases.As the alveolar epithelial typeⅡcells to mesenchymal cell transformation(EMT) is an important factors of pulmonary fibrosis,so we adopted A549 cells in this experiment and used transforming growth factor induced EMT to occur in A549 cells to study the effect of Li Tao Kang Xian Fang droplet in EMT.Real-time PCR,Western-blot and ELISA was introduced to define the biology basic of Li Tao Kang Xian Fang droplet playing a anti- fibrosis role by controling EMT.
Methods:Different concentrations of Li Tao Kang Xian Fang was used to intervene A549 cells in vitro.ELISA were used to show the retative contents of the TGF-β1 in A549 cells.We used TGF-β1 to induce the occurrence of EMT.The collagenⅠand collagenⅢmRNA level was monitored by real-time PCR,the protein level of phosphorylation Erk1/2 were examined by western blot analysis. Cell apoptosis and cell cycle distribution were determined by flow cytometry.The protein level of phosphorylation Erk1/2 were examined by western blot analysis.
Results:Our data showed that contents of the TGF-β1 ruduced after 24h intervention of different concentrations of Li Tao Kang Xian Fang.In TGF-β1-induced cells,vimentin espression have a sharp increase but cytokeratina espression have a relative reduction.The level of collagenⅠandⅢshow Significantly higher.By intervening of different concentrations of Li Tao Kang Xian Fang,vimentin espression was significantly lower,yet cytokeratina espression was significantly higher than that in the model group.Meantime,It bring a obvious reduction in espression of collagenⅠ、Ⅲand phosphorylation Erk1/2.
Conclusion:Li Tao Kang Xian Fang can drop the EMT rates of TGF-β1 -induced A549 cells,thereby ruduce ACEⅡcells to epithelial cells.It lead to a reduction of lung fibroblast production,to inhibit the occurrence of pulmonary fibrosis,so as to achieve an anti- fibrosis role.The possible mechanism maybe by reducing the transforming growth factor(TGF-β) releasion,interveningⅠandⅢcollagen mRNA expression,and affecting cell phosphorylation Erk1/ 2 expression.
引文
[1]Hogg JC,Chu F,Utokaparch S,Woods R,Elliott WM,Buzatu L,Cherniack RM,Rogers RM,Sciurba FC,Coxson HO,Pare PD.The nature of small-airway obstruction in chronic obstructive pulmonary disease.N Engl J Med 2004;350:2645-53
[2]A T S and E R S.American Thoracic Society /European Respiratory Society international nmlfidisc iplinary consensus classification of the idiopathic interstitial pneumonia.Am J Respir Crit Care Med,2002,165(2):277-304
[3]中华医学会呼吸病学分会.特发性肺(间质)纤维化诊断和治疗指南(草案).中华呼吸结核杂志,2002,25(4):11-18
[4]陈兴无,徐军,钟南山.上皮损伤和肺纤维化.国外医学呼吸系统分册,2002,(2):57-59
[5]Massaro D.,ed.Lung cell Biology.Marcel Dekker,Inc,1989;14
[6]Lan HY.Tubular epithelial-myofibroblast transdifferentiation mechanisms in proximal tubule cells.Curr Opin Nephrol Hypertens 2003;12:25-9
[7]Nicolas FJ,Lehmann K,Warne PH,Hill CS,Downward J.Epithelial to mesenchymal transition in Madin-Darby canine kidney cells is accompanied by down-regulation of Smad3 expression,leading to resistance to transforming growth factor-beta-induced growth arrest.J Biol Chem 2003;278:3251-6
[8]Do JY.Epithelial to mesenchymal transition in CAPD patients.Yeungnam Univ J Med 2006;23:10-8
[9]徐古成.超声雾化吸入法治疗毛细支气管炎54例疗效分析.新医学,1986,17(8):410
[1]DunnillMS.Pulmonaryfibrosis.Histopathology,1990,16(4):321
[2]Perez-Arellano JL,Barrios MN,MartinT,et al.Hydrolytic enzyme of the alveolar macrophage in diffuse pulmonary interstitial disease.RespirMed,1996,90(3):159
[3]Meliconi R,Andreone P,Fasano L,et al.Incidence of the patitis C virus infection in Italian patients with IPF.Thorax,1996,51(3):315
[4]谷丽,朱元珏.特发性肺间质纤维化与肺肌成纤维细胞[J].国外医学呼吸系统分册,2005,25(5):361
[5]Brigham C Willis,JanieeM,Liebler,et al.Induction of epithelialmesenehymaltransitionin alveolar epithelialcels by transforming growth factor-betal[J].Ameriean Journalof Pathology,2005,166:1321
[6]SimePJ.O ReillyKMA.Fibrosisofthelungandothertissues:neweoneePtsinParhoge nesiandtreatlnent.ClinImmunol2001;99(3):308-319
[7]Mapel DW,Samet JM,Coultes DB.Corticosteroids and the treatment of idiopathic pulmonary fibrosis:Past,present and future[J].Chest,1996,110(4):1058-1067
[8]DouglasWW,Ryu JH,Bjoraker JA,et al.Colchicine versus prednisone as treatment of usual interstitial pneumonia[J].Mayo Clin Proc,1997,72(3):201-209
[9]Cornelissen AM,Von den Hoff JW,Maltha JC,et al.Effects of in2terferons in proliferation and collage synthesis of rat palatalwound fibroblasts[J].Arch OralBiol,1999,44(7):541-547
[10]Coker RK,Laurent GJ.Pulmonary fibrosis:cytokines in the balance[J].Eur Resp ir J,1998,11(6):1218-1221
[11]Borok Z,Buhl R,Grimes GJ,et al.Effect of glutathione aerosol on oxidant-antioxidant imbalance in idiopathic pul-monary fibrosis[J].Lancet,1991,338(8761):215-216
[12]0gushi F,Endo T,Tani K,et al.Decreased proistaglandin E2synthesis by lung fibroblasts isolated from ratswith bleomycin-induced lung fibrosis[J].Int J Exp Patho,1999,80(1):41-49
[13]陈金亮,王殿华.络病理论与肺纤维化的关系探析[J].中医药学刊,2004,22(3):31-40
[14]仝润芍.血府逐淤汤加减治疗弥漫性间质性肺炎46例[J].河南中医,1996,16(4):233
[15]邱志楠,潘俊辉.中西医结合治疗特发性肺间质纤维化68例临床观察[J].中国中医急症,2002,11(2):40
[16]王新华,张弘.特发性肺纤维化的中西医治疗[J].贵阳中医学院学报,2000,22(4):21-23
[17]郭淑珍.肺痿病机及辩证初探[J].新中医,1994,11:5-6
[18]张天嵩,董洪涛,陈跃来.特发性肺纤维化的中医病机探讨[J].中医函授通讯,1999,18(3):14-15
[19]宋建平.肺纤维化的中医药研究概况[J].中国中医药信息杂志,1999,5(6):13-14
[20]张纾难,晁恩祥.对急性型特发性肺纤维化治疗难点的思考[J].中国中医急症1998,7(4):176-178.
[21]王海彤,武维屏.中医药治疗弥漫性肺间质纤维化信息讨论[J].中国中医药信息杂志,1996,3(7):25-27.
[22]姜良铎,张晓梅,肖培新.特发性肺间质纤维化的病因病机探讨[J].中华中医药杂志,2008,11,23:(11):40
[23]崔红生,武维屏,姜良铎.毒损肺络与肺间质纤维化[J].中医杂志,2007,48,(9):11-15
[24]蔡代仲,翟华强.论上盛下虚为肺纤维化基本病机[J].中国中医药信息杂志,2000,11(9):31-33
[25]宋建平.《金匮要略》所论短气与特发性肺纤维化[J].南京中医药大学学报,1998,11(6):28-31
[26]李素云,朱佳.抗纤颗粒治疗弥漫性肺间质纤维化及其对细胞因子的影响[J].中国中医药信息杂志,2002,9(5):31-33
[27]蒋云峰.黄芪桃红汤治疗特发性肺纤维化24例[J].吉林中医药,2003,23(11):16-19
[28].杨和春.浅谈肺系疾病的上盛下虚证治[J].湖北中医杂志,1989,(5):33-34
[29]陈芳,吴符火.中药抗炎治疗肺纤维化的综述[J].福建中医学院学报2006,16(5):12
[30]孔祥文.特发性肺纤维化的中医治疗[J].现代中西医结合杂志,2003,12(1):45-46
[31]王海彤,武维屏.中医药治疗弥漫性肺间质纤维化信息讨论[J].中国中医药信息杂志,1996,3(7):25-26
[32]智屹惠.曹世宏教授论治肺间质纤维化[J].南京中医药大学学报,2001,17:(3):22-25
[33]彭玉华.特发性肺纤维化中医药治疗思路与方法[J].中医药学刊,2003,21(10):55-57
[34]王书臣,崔天红.弥漫性肺间质性肺炎62例[J].中医杂志,1998,39(9):32
[35]张天嵩,马君.赵子贤辨治弥漫性肺间质纤维化经验[J].浙江中医杂志,1998,33(3):39
[36]曹世宏.论治肺间质纤维化[J].南京中医药大学学报(自然科学版),2001,17(3):44-47
[37]张纾难,李兰群.益气润肺化淤解毒法治疗特发性肺纤维化临床研究[J].北京中医药大学学报,1999,22(3):57-60
[38]杨效华,张晓梅.肺间质纤维化的中医药治疗[J].中国临床医生,2002,30(6):18-21
[39]张天嵩,赵子贤,等.补气通肺汤治疗特发性肺纤维化12例[J].浙江中医杂志,1999,34(2):131-140
[40]刘薇中医结合治疗特发性肺间质纤维化32例临床观察[J].中医杂志,2005.46(9):675-676
[41]刘建博,刘小虹,等.肺康颗粒治疗弥漫性肺间质纤维化临床观察[J].中国中医急症,2001,10(2):66-69
[42]刘三都,鲍崇忠.肺乐宁抗结核性肺纤维化临床研究[J].贵阳中医学院学报,1999,21(4):11-12
[43]欧阳修河,胡翠花.川芎嗪治疗特发性肺纤维化临床观察[J].实用医学杂志,1998,14(7):22-26
[44]靳长俊,辛洪涛,林殿杰,等.芪丹颗粒剂治疗肺间质纤维化105例临床研究[J].中医杂志,2005,46(8):595-597
[45]邱志楠,潘俊辉.中西医结合治疗特发性肺间质纤维化68例临床观察[J].中国中医急症,2002,11(2):55-57
[46]唐玲华,李春生.特发性弥漫性肺间质纤维化13例治疗报告[J].中医杂志,1997,38(1):31-40
[47]韩雪友.中西医结合治疗小儿自发性肺炎80例对照观察[J].四川中医,1991,20:21
[1]Venkatesan N,Roughley P J,Ludwig M S.Proteoglycan expression in bleomycin lung fibroblasts:role of transforming growth faetor-beta(1)and interferon-gamma[J].Am J Physiol Lung Cell Mol Physiol,2002,283(4):806
[2]Schnaper HW,Hayashida T,Hubchak SC et al.TGF-|3 signal transduction and mesangial cell fibrogenesisJ.Am J Physiol Rehal Physiol,2003,284(2):F243-52
[3]Sim PJ,Zhou X,Frank Let al.Adenovector-mediated gene transfer of active transforming growth factor-131 induces prolonged severe fibrosis in rat lung[J].J Clin Invest,1997,100(4):76876
[4]Thiery JP,Sleeman JP.Complex networks orchestrate epithelial-mesenchymal transitions[J].Nat RevMol Cell Biol,2006,7(2):1312142
[5]Will is BC.,duBois RM,Borok Z.Ep ithelial origin of myofibroblasts during fibrosis in the lung[J].Proc Am Thorac Soc,2006,3(4):3772382
[6]WinterMC.,Shasby SS,Ries DR,et al.PAR2 activation inter-rupts E-cadher in adhesion and comp romises the airway epithelial barrier:protective effect of β-agonists[J].Am J Physiol Lung CellMol Physiol,2006,291(4):L6282L635
[7]SelmanM,Pardo A.Role of ep ithelial cells in idiopathic pulmonary fibrosis:from innocent targets to serial killers[J].Proc Am Thorac Soc,2006,3(4):3642372
[8]Lee JM,Dedhar S,Kalluri et al.Theepithelial-mesenchymal transition:ne insights in signaling,development,and disease[J].J Cell Biol,2006,172(7):9732981
[9]Mazzali M,Kipari T,Ophascharoensuk V,et al.Osteopontin-amolecule for all seasons[J],Q J Med,2002,95(1):3213
[10]侯杰,戴令娟.川芎嗪、丹参治疗大鼠肺纤维化对Ⅰ、Ⅲ型前胶原基因表达的影响.中华结核和呼吸杂志,1999。22(1):43-44
[11]何玉先,刘秉慈.实验性矽肺纤维化组织中Ⅰ、Ⅲ型前胶原基因的表达.基础医学与临床,1994,14(6):43-46
[12]Hou J,Dai L,Huang M,Cai H.The therapeutic effect of ligustrazin and salvia miltiorrhiza on the gene expression of alphal(Ⅰ) and alphal(Ⅲ) procollagen in rat pulmonary fibrosis.Zhonghua Jie He He Hu Xi Za Zhi.1999 Jan;22(1):43-51
[13]Palosaari H,Tasanen K,Risteli J,et al.Baseline expression and effect of TGF-beta 1 on type Ⅰ and Ⅲ collagen mRNA and protein synthesis in human odontoblasts and pulp cells in vitro.Calcif Tissue Int.2001 Feb;68(2):122
[14]Hennig M,Yip-Schneider MT,Klein P,etal.Ethanol-TGF1 pha-MEK Signal ing Promotes Growth of Human Hepatocellular Carcinoma.J Surg Res.2008 Dec 13
[15]Hung KY,Chen CT,Huang JW,et al.Dipyridamole inhibits TGF-beta-induced collagen gene expression in human peritoneal mesothelial cells.Kidney Int.2001 Oct;60(4):1249-57
[16]Tatsukawa T,Chimura T,Miyakawa H,et al.Involvement of basal protein kinase C and extracellular signal-regulated kinase 1/2activities in constitutive internalization of AMPA receptors in cerebellar Purkinje cells.J Neurosci.2006 May 3;26(18):4820
[17]Bashkin P,Neufeld G,Gitay-Goren H,et al.Release of cell surface-associated basic fibroblast growth factor by glycosy phosphatidylinositol-specific phospholipase C.J Cell Physiol.1992 Apr;151(1):126-137
[18]Agostini C.,Siviero M,Semenzato G.Immune effector cells in idiopathic pulmonary fibrosis.Curr Opin Pulm Med,1997,3:348-355
[19]Robert AB,Flanders KC.,Heine UI,et al.Transforming growth factor beta:multifunctional regulator of difierentiation and development.Phi los Trans R Soc Le nd B Biol Sci,1990,327:145-154
[20]Roberts AB,McCune BK,Sporn MB.TGF-B regulation of extracellular matrix.Kidney Int,1992,41:557-559
[21]Linnala A,Kinnula V,LaitinenLA,et al.Transforming growth factor-beta regu lates the expression of fibronectin and tenascin in BEAS 2B human bronchial epithelial cells.Am J Respir Cell MolBiol,1995,13:578-585
[22]Zhang K,Kat hlee n C,Flla nder S,et al.Cellular loca tion of transforming growth f ac tor～1 exp ression in bleomycin-induced pulmonary fibrosis[J].AmJ Pathol,1995,4(2):352.
[23]Gurujeyala shmi G,Giri SN.Molecular mechanisns of ant if ibrot ic effects of interfe ro n gamma in bleom ycinmo use model of lung fibrosis:Down regulat ion TGF2B and procol lagen I and mgene expyes Sion[J].Exp Lung Res,1995,21(11):791
[24]You GQ,Fu P,Xie XS,et al.Effects of piperazine ferulate on TGF-bet al-induced renal interstitial fibroblas activation.Sichuan Da Xue Xue Bao Yi Xue Ban.2008 Sep;39(5):736-9,762.
[25]Peng Y,Liu H,Liu F,et al.Trogl itazone inhibits synthesis of transforming growth factor-bet al and reduces matrix production in human peritoneal mesothelial cells.Nephrology(Carlton).2006 Dec;11(6):516-23.
[1]朱元珏.特发性肺间质纤维化[J].现代呼吸病学,1997,7(9):721
[2]施焕中.林江涛.肺脏免疫学及免疫相关性疾病.人民卫生出版社.2006.738-745
[3]Francis HY Green MD Overview of Pulnonary fibrosis.Chest.2002;122;334
[4]Kaminski N,BelPerioJA,Bitterman PB,etal.IdioPathic Pulmonaryfibrosis.AmJ Respir Cell MolBiol.2003;29(3):91
[5]Bauragartner KB,SametJM,Coultas DB etal.occupational And environmental Risk factors for idiopathic Pulmonary fiborsis:a multicenter case-control study.AmJ Epidemiol.2000;152:307
[6]孙铁英,林嘉滨,张洪胜,等.48例慢性肺间质疾病临床特征分析及肺功能分析[J].北京医学,2002,24(4):232-234.
[7]Piquet PF,Collart MA,Grau GE,et al.Tumor necrosis factor /cachecctin plays a key role in bleomycin induced pneumopathy and fibrosis.J Exp Med,1989,170:655。663.
[8]Fu jit a M,Shannon IM,M orikaw a O,et al.Overexpression Of tumor necrosis factor2-lpha diminishes pulmonary fibrosis Induced by bleomycin or transforming growth factor-beta[J].Am J Respir Cell Molbiol,2003,29(6):669-676.
[9]Kunkel SL,Chensue SW,Lukacs N,etal.Cytokine phenotype serve as a paradigm for experimental immune-mediated.AMJ Respir Cell Mol Biol.2003,29:S63-S66
[10]Lukacs,NW,Hogaboam,C,Chensue,SW,etal.TyPy,PeZcytokineParadi ge PoregrssionofPulmonary fiborsis.Chest.2001,20:49-54
[11]Michael,Pkeane,JohnAe,talatnuate,cininduced.Pulmonaryboris ,Jphsyiolng Cellmol Physiol.2001,281(1):92-97
[12]Hashimo,to Landlinduemy of broblastic PhenotyPefo human lnug fibroblasst through cunN2 temrinal Palhway.Jalelgry Clin Immunol,2001,107(6):1001-1008
[13]陈莹,董静,陈杰等.γ干扰素对矽肺大鼠肺脏白介素-4和转化生长因子β1蛋白表达的影响[J].中华劳动卫生职业病杂志.2004,22(5):350—353
[14]Szabo SJ,KjmST,CostaGLetal.An oveltran scriPtionfaclor,T-be directs Th1 lineage commitmen cell.2000,100(6):655-669
[15]HuauxF,LiuT,McGaryB,etal.Dualrolesof1L.4inlunginju and fibrosisIJ].Jlmmunlo.2003,170(4):2083-2092
[16]Jakubzick C,ChoiES JoshiBH,da1,Thereuti catenuationof Pulmonaryfibors is viataegrtingof IL andIL13-responsivc cell sj11Jmmunol,2003,17,1(5):2684-2693
[17]Postlct hwaite AE,SayerJM.Fibroblastchemo taxi sinduction by humane recombinant interleukin-4.Identifi Cation by synthe tic petide analys of chemotactic domains residinginam in acid sequences70-88 and 89-122.J ClinInv 1991,87:2147-2152
[18]Paul WE.Interleukin-4 a Prototypic immune oreguly ymPhokine.Blood.1991,77:1589-1807
[19]Lee CJ,Homer RJ,ZhuZ,et al.Characterization of the effct interleukin-13 induce tissue fiborsis by seIeCtielvy stimulating and activatin gorth transforming groth hacf otrbeta(1).J ExP Mes.2001,194(6):89-82
[20]Kuroki M,Noguchi Y,Shimono,et al.TGF-betal as an enhance of Fas-mediated apoptosis oflung epithelial cells,J Immunol.2002,168:6470-6478
[21]Song M,He B,Qiu Z.Expressisons of TNF-a,PFGF in alveolar type Ⅱ epithelial cells of tats with bleomcy in-induces Pulmonary cells inbleomc in-induced pulmontay fiborsis.Zhonghua Jiehe Huxi Zazhil998,21(4):221-223
[22]American Thoracic Society.Idiopathic pulmonary fibrosis:diagnosisandtreatment.Internationalconsensus statemen.American Thoracic Society(ATS),and the European Respiratory Society(ERS)[J].A mJ R espir Crit Care Med,2000,161(2 Pt):646-664
[23]Wang R,Ibarra-Sunga 0,Verlinski L,et al.Abrogation of bleomycin-induced epithelial apoptosis and lung fibrosis by captopril or by a caspase inhibitor.Am J Physiol Lung Cell Mol Physiol.2000;279(1):L143-151
[24]Robert J,Mason,Marvin Ⅰ,et al.Pharmacological therapy for idiopathic pulmonary fibrosis.Am J Respir Crit Card Med.1999;160(5pt 1):1771-1777
[25]李京红,何冰,翁保迎.转化生长因子-β1单克隆抗体对大鼠肺纤维化的治疗观察.中华结核和呼吸杂志.1997;20(6):347-349
[26]LossosIS,Breuer R,Shriki M,et al.Peribronchial lymphocyte activation,in lung injury.LifeSci.1998;63(13):1183-1193.
[27]Sciavolino PJ,Lee TH,Vilcek J.Interferon-beta induces metalloproteinase mRNA expression in human fibroblasts.Role of activator protein-1.J Biol Chem.1994;269(34):21627-21634
[28]王海涛,刘吴,颜京霞,等.N-乙酰-L-半胱氨酸对染矽尘大鼠肺间质成纤维细胞INF-Γ表达的影响.第三军医大学学报,2005,27(19):2003
[29]王海涛,高俊玲,田艳霞,等.N-乙酰-L-半胱氨酸对矽肺模型大鼠肺泡巨噬细胞基质金属蛋白酶2、9表达的影响.中华结核和呼吸杂志,2006,29(1):63-64
[2]A T S and E R S.American Thoracic Society /European Respiratory Society international nmlfidisc iplinary consensus classification of the idiopathic interstitial pneumonia.Am J Respir Crit Care Med,2002,165(2):277-304
[3]中华医学会呼吸病学分会.特发性肺(间质)纤维化诊断和治疗指南(草案).中华呼吸结核杂志,2002,25(4):11-18
[4]陈兴无,徐军,钟南山.上皮损伤和肺纤维化.国外医学呼吸系统分册,2002,(2):57-59
[5]Massaro D.,ed.Lung cell Biology.Marcel Dekker,Inc,1989;14
[6]Lan HY.Tubular epithelial-myofibroblast transdifferentiation mechanisms in proximal tubule cells.Curr Opin Nephrol Hypertens 2003;12:25-9
[7]Nicolas FJ,Lehmann K,Warne PH,Hill CS,Downward J.Epithelial to mesenchymal transition in Madin-Darby canine kidney cells is accompanied by down-regulation of Smad3 expression,leading to resistance to transforming growth factor-beta-induced growth arrest.J Biol Chem 2003;278:3251-6
[8]Do JY.Epithelial to mesenchymal transition in CAPD patients.Yeungnam Univ J Med 2006;23:10-8
[9]徐古成.超声雾化吸入法治疗毛细支气管炎54例疗效分析.新医学,1986,17(8):410
[1]DunnillMS.Pulmonaryfibrosis.Histopathology,1990,16(4):321
[2]Perez-Arellano JL,Barrios MN,MartinT,et al.Hydrolytic enzyme of the alveolar macrophage in diffuse pulmonary interstitial disease.RespirMed,1996,90(3):159
[3]Meliconi R,Andreone P,Fasano L,et al.Incidence of the patitis C virus infection in Italian patients with IPF.Thorax,1996,51(3):315
[4]谷丽,朱元珏.特发性肺间质纤维化与肺肌成纤维细胞[J].国外医学呼吸系统分册,2005,25(5):361
[5]Brigham C Willis,JanieeM,Liebler,et al.Induction of epithelialmesenehymaltransitionin alveolar epithelialcels by transforming growth factor-betal[J].Ameriean Journalof Pathology,2005,166:1321
[6]SimePJ.O ReillyKMA.Fibrosisofthelungandothertissues:neweoneePtsinParhoge nesiandtreatlnent.ClinImmunol2001;99(3):308-319
[7]Mapel DW,Samet JM,Coultes DB.Corticosteroids and the treatment of idiopathic pulmonary fibrosis:Past,present and future[J].Chest,1996,110(4):1058-1067
[8]DouglasWW,Ryu JH,Bjoraker JA,et al.Colchicine versus prednisone as treatment of usual interstitial pneumonia[J].Mayo Clin Proc,1997,72(3):201-209
[9]Cornelissen AM,Von den Hoff JW,Maltha JC,et al.Effects of in2terferons in proliferation and collage synthesis of rat palatalwound fibroblasts[J].Arch OralBiol,1999,44(7):541-547
[10]Coker RK,Laurent GJ.Pulmonary fibrosis:cytokines in the balance[J].Eur Resp ir J,1998,11(6):1218-1221
[11]Borok Z,Buhl R,Grimes GJ,et al.Effect of glutathione aerosol on oxidant-antioxidant imbalance in idiopathic pul-monary fibrosis[J].Lancet,1991,338(8761):215-216
[12]0gushi F,Endo T,Tani K,et al.Decreased proistaglandin E2synthesis by lung fibroblasts isolated from ratswith bleomycin-induced lung fibrosis[J].Int J Exp Patho,1999,80(1):41-49
[13]陈金亮,王殿华.络病理论与肺纤维化的关系探析[J].中医药学刊,2004,22(3):31-40
[14]仝润芍.血府逐淤汤加减治疗弥漫性间质性肺炎46例[J].河南中医,1996,16(4):233
[15]邱志楠,潘俊辉.中西医结合治疗特发性肺间质纤维化68例临床观察[J].中国中医急症,2002,11(2):40
[16]王新华,张弘.特发性肺纤维化的中西医治疗[J].贵阳中医学院学报,2000,22(4):21-23
[17]郭淑珍.肺痿病机及辩证初探[J].新中医,1994,11:5-6
[18]张天嵩,董洪涛,陈跃来.特发性肺纤维化的中医病机探讨[J].中医函授通讯,1999,18(3):14-15
[19]宋建平.肺纤维化的中医药研究概况[J].中国中医药信息杂志,1999,5(6):13-14
[20]张纾难,晁恩祥.对急性型特发性肺纤维化治疗难点的思考[J].中国中医急症1998,7(4):176-178.
[21]王海彤,武维屏.中医药治疗弥漫性肺间质纤维化信息讨论[J].中国中医药信息杂志,1996,3(7):25-27.
[22]姜良铎,张晓梅,肖培新.特发性肺间质纤维化的病因病机探讨[J].中华中医药杂志,2008,11,23:(11):40
[23]崔红生,武维屏,姜良铎.毒损肺络与肺间质纤维化[J].中医杂志,2007,48,(9):11-15
[24]蔡代仲,翟华强.论上盛下虚为肺纤维化基本病机[J].中国中医药信息杂志,2000,11(9):31-33
[25]宋建平.《金匮要略》所论短气与特发性肺纤维化[J].南京中医药大学学报,1998,11(6):28-31
[26]李素云,朱佳.抗纤颗粒治疗弥漫性肺间质纤维化及其对细胞因子的影响[J].中国中医药信息杂志,2002,9(5):31-33
[27]蒋云峰.黄芪桃红汤治疗特发性肺纤维化24例[J].吉林中医药,2003,23(11):16-19
[28].杨和春.浅谈肺系疾病的上盛下虚证治[J].湖北中医杂志,1989,(5):33-34
[29]陈芳,吴符火.中药抗炎治疗肺纤维化的综述[J].福建中医学院学报2006,16(5):12
[30]孔祥文.特发性肺纤维化的中医治疗[J].现代中西医结合杂志,2003,12(1):45-46
[31]王海彤,武维屏.中医药治疗弥漫性肺间质纤维化信息讨论[J].中国中医药信息杂志,1996,3(7):25-26
[32]智屹惠.曹世宏教授论治肺间质纤维化[J].南京中医药大学学报,2001,17:(3):22-25
[33]彭玉华.特发性肺纤维化中医药治疗思路与方法[J].中医药学刊,2003,21(10):55-57
[34]王书臣,崔天红.弥漫性肺间质性肺炎62例[J].中医杂志,1998,39(9):32
[35]张天嵩,马君.赵子贤辨治弥漫性肺间质纤维化经验[J].浙江中医杂志,1998,33(3):39
[36]曹世宏.论治肺间质纤维化[J].南京中医药大学学报(自然科学版),2001,17(3):44-47
[37]张纾难,李兰群.益气润肺化淤解毒法治疗特发性肺纤维化临床研究[J].北京中医药大学学报,1999,22(3):57-60
[38]杨效华,张晓梅.肺间质纤维化的中医药治疗[J].中国临床医生,2002,30(6):18-21
[39]张天嵩,赵子贤,等.补气通肺汤治疗特发性肺纤维化12例[J].浙江中医杂志,1999,34(2):131-140
[40]刘薇中医结合治疗特发性肺间质纤维化32例临床观察[J].中医杂志,2005.46(9):675-676
[41]刘建博,刘小虹,等.肺康颗粒治疗弥漫性肺间质纤维化临床观察[J].中国中医急症,2001,10(2):66-69
[42]刘三都,鲍崇忠.肺乐宁抗结核性肺纤维化临床研究[J].贵阳中医学院学报,1999,21(4):11-12
[43]欧阳修河,胡翠花.川芎嗪治疗特发性肺纤维化临床观察[J].实用医学杂志,1998,14(7):22-26
[44]靳长俊,辛洪涛,林殿杰,等.芪丹颗粒剂治疗肺间质纤维化105例临床研究[J].中医杂志,2005,46(8):595-597
[45]邱志楠,潘俊辉.中西医结合治疗特发性肺间质纤维化68例临床观察[J].中国中医急症,2002,11(2):55-57
[46]唐玲华,李春生.特发性弥漫性肺间质纤维化13例治疗报告[J].中医杂志,1997,38(1):31-40
[47]韩雪友.中西医结合治疗小儿自发性肺炎80例对照观察[J].四川中医,1991,20:21
[1]Venkatesan N,Roughley P J,Ludwig M S.Proteoglycan expression in bleomycin lung fibroblasts:role of transforming growth faetor-beta(1)and interferon-gamma[J].Am J Physiol Lung Cell Mol Physiol,2002,283(4):806
[2]Schnaper HW,Hayashida T,Hubchak SC et al.TGF-|3 signal transduction and mesangial cell fibrogenesisJ.Am J Physiol Rehal Physiol,2003,284(2):F243-52
[3]Sim PJ,Zhou X,Frank Let al.Adenovector-mediated gene transfer of active transforming growth factor-131 induces prolonged severe fibrosis in rat lung[J].J Clin Invest,1997,100(4):76876
[4]Thiery JP,Sleeman JP.Complex networks orchestrate epithelial-mesenchymal transitions[J].Nat RevMol Cell Biol,2006,7(2):1312142
[5]Will is BC.,duBois RM,Borok Z.Ep ithelial origin of myofibroblasts during fibrosis in the lung[J].Proc Am Thorac Soc,2006,3(4):3772382
[6]WinterMC.,Shasby SS,Ries DR,et al.PAR2 activation inter-rupts E-cadher in adhesion and comp romises the airway epithelial barrier:protective effect of β-agonists[J].Am J Physiol Lung CellMol Physiol,2006,291(4):L6282L635
[7]SelmanM,Pardo A.Role of ep ithelial cells in idiopathic pulmonary fibrosis:from innocent targets to serial killers[J].Proc Am Thorac Soc,2006,3(4):3642372
[8]Lee JM,Dedhar S,Kalluri et al.Theepithelial-mesenchymal transition:ne insights in signaling,development,and disease[J].J Cell Biol,2006,172(7):9732981
[9]Mazzali M,Kipari T,Ophascharoensuk V,et al.Osteopontin-amolecule for all seasons[J],Q J Med,2002,95(1):3213
[10]侯杰,戴令娟.川芎嗪、丹参治疗大鼠肺纤维化对Ⅰ、Ⅲ型前胶原基因表达的影响.中华结核和呼吸杂志,1999。22(1):43-44
[11]何玉先,刘秉慈.实验性矽肺纤维化组织中Ⅰ、Ⅲ型前胶原基因的表达.基础医学与临床,1994,14(6):43-46
[12]Hou J,Dai L,Huang M,Cai H.The therapeutic effect of ligustrazin and salvia miltiorrhiza on the gene expression of alphal(Ⅰ) and alphal(Ⅲ) procollagen in rat pulmonary fibrosis.Zhonghua Jie He He Hu Xi Za Zhi.1999 Jan;22(1):43-51
[13]Palosaari H,Tasanen K,Risteli J,et al.Baseline expression and effect of TGF-beta 1 on type Ⅰ and Ⅲ collagen mRNA and protein synthesis in human odontoblasts and pulp cells in vitro.Calcif Tissue Int.2001 Feb;68(2):122
[14]Hennig M,Yip-Schneider MT,Klein P,etal.Ethanol-TGF1 pha-MEK Signal ing Promotes Growth of Human Hepatocellular Carcinoma.J Surg Res.2008 Dec 13
[15]Hung KY,Chen CT,Huang JW,et al.Dipyridamole inhibits TGF-beta-induced collagen gene expression in human peritoneal mesothelial cells.Kidney Int.2001 Oct;60(4):1249-57
[16]Tatsukawa T,Chimura T,Miyakawa H,et al.Involvement of basal protein kinase C and extracellular signal-regulated kinase 1/2activities in constitutive internalization of AMPA receptors in cerebellar Purkinje cells.J Neurosci.2006 May 3;26(18):4820
[17]Bashkin P,Neufeld G,Gitay-Goren H,et al.Release of cell surface-associated basic fibroblast growth factor by glycosy phosphatidylinositol-specific phospholipase C.J Cell Physiol.1992 Apr;151(1):126-137
[18]Agostini C.,Siviero M,Semenzato G.Immune effector cells in idiopathic pulmonary fibrosis.Curr Opin Pulm Med,1997,3:348-355
[19]Robert AB,Flanders KC.,Heine UI,et al.Transforming growth factor beta:multifunctional regulator of difierentiation and development.Phi los Trans R Soc Le nd B Biol Sci,1990,327:145-154
[20]Roberts AB,McCune BK,Sporn MB.TGF-B regulation of extracellular matrix.Kidney Int,1992,41:557-559
[21]Linnala A,Kinnula V,LaitinenLA,et al.Transforming growth factor-beta regu lates the expression of fibronectin and tenascin in BEAS 2B human bronchial epithelial cells.Am J Respir Cell MolBiol,1995,13:578-585
[22]Zhang K,Kat hlee n C,Flla nder S,et al.Cellular loca tion of transforming growth f ac tor～1 exp ression in bleomycin-induced pulmonary fibrosis[J].AmJ Pathol,1995,4(2):352.
[23]Gurujeyala shmi G,Giri SN.Molecular mechanisns of ant if ibrot ic effects of interfe ro n gamma in bleom ycinmo use model of lung fibrosis:Down regulat ion TGF2B and procol lagen I and mgene expyes Sion[J].Exp Lung Res,1995,21(11):791
[24]You GQ,Fu P,Xie XS,et al.Effects of piperazine ferulate on TGF-bet al-induced renal interstitial fibroblas activation.Sichuan Da Xue Xue Bao Yi Xue Ban.2008 Sep;39(5):736-9,762.
[25]Peng Y,Liu H,Liu F,et al.Trogl itazone inhibits synthesis of transforming growth factor-bet al and reduces matrix production in human peritoneal mesothelial cells.Nephrology(Carlton).2006 Dec;11(6):516-23.
[1]朱元珏.特发性肺间质纤维化[J].现代呼吸病学,1997,7(9):721
[2]施焕中.林江涛.肺脏免疫学及免疫相关性疾病.人民卫生出版社.2006.738-745
[3]Francis HY Green MD Overview of Pulnonary fibrosis.Chest.2002;122;334
[4]Kaminski N,BelPerioJA,Bitterman PB,etal.IdioPathic Pulmonaryfibrosis.AmJ Respir Cell MolBiol.2003;29(3):91
[5]Bauragartner KB,SametJM,Coultas DB etal.occupational And environmental Risk factors for idiopathic Pulmonary fiborsis:a multicenter case-control study.AmJ Epidemiol.2000;152:307
[6]孙铁英,林嘉滨,张洪胜,等.48例慢性肺间质疾病临床特征分析及肺功能分析[J].北京医学,2002,24(4):232-234.
[7]Piquet PF,Collart MA,Grau GE,et al.Tumor necrosis factor /cachecctin plays a key role in bleomycin induced pneumopathy and fibrosis.J Exp Med,1989,170:655。663.
[8]Fu jit a M,Shannon IM,M orikaw a O,et al.Overexpression Of tumor necrosis factor2-lpha diminishes pulmonary fibrosis Induced by bleomycin or transforming growth factor-beta[J].Am J Respir Cell Molbiol,2003,29(6):669-676.
[9]Kunkel SL,Chensue SW,Lukacs N,etal.Cytokine phenotype serve as a paradigm for experimental immune-mediated.AMJ Respir Cell Mol Biol.2003,29:S63-S66
[10]Lukacs,NW,Hogaboam,C,Chensue,SW,etal.TyPy,PeZcytokineParadi ge PoregrssionofPulmonary fiborsis.Chest.2001,20:49-54
[11]Michael,Pkeane,JohnAe,talatnuate,cininduced.Pulmonaryboris ,Jphsyiolng Cellmol Physiol.2001,281(1):92-97
[12]Hashimo,to Landlinduemy of broblastic PhenotyPefo human lnug fibroblasst through cunN2 temrinal Palhway.Jalelgry Clin Immunol,2001,107(6):1001-1008
[13]陈莹,董静,陈杰等.γ干扰素对矽肺大鼠肺脏白介素-4和转化生长因子β1蛋白表达的影响[J].中华劳动卫生职业病杂志.2004,22(5):350—353
[14]Szabo SJ,KjmST,CostaGLetal.An oveltran scriPtionfaclor,T-be directs Th1 lineage commitmen cell.2000,100(6):655-669
[15]HuauxF,LiuT,McGaryB,etal.Dualrolesof1L.4inlunginju and fibrosisIJ].Jlmmunlo.2003,170(4):2083-2092
[16]Jakubzick C,ChoiES JoshiBH,da1,Thereuti catenuationof Pulmonaryfibors is viataegrtingof IL andIL13-responsivc cell sj11Jmmunol,2003,17,1(5):2684-2693
[17]Postlct hwaite AE,SayerJM.Fibroblastchemo taxi sinduction by humane recombinant interleukin-4.Identifi Cation by synthe tic petide analys of chemotactic domains residinginam in acid sequences70-88 and 89-122.J ClinInv 1991,87:2147-2152
[18]Paul WE.Interleukin-4 a Prototypic immune oreguly ymPhokine.Blood.1991,77:1589-1807
[19]Lee CJ,Homer RJ,ZhuZ,et al.Characterization of the effct interleukin-13 induce tissue fiborsis by seIeCtielvy stimulating and activatin gorth transforming groth hacf otrbeta(1).J ExP Mes.2001,194(6):89-82
[20]Kuroki M,Noguchi Y,Shimono,et al.TGF-betal as an enhance of Fas-mediated apoptosis oflung epithelial cells,J Immunol.2002,168:6470-6478
[21]Song M,He B,Qiu Z.Expressisons of TNF-a,PFGF in alveolar type Ⅱ epithelial cells of tats with bleomcy in-induces Pulmonary cells inbleomc in-induced pulmontay fiborsis.Zhonghua Jiehe Huxi Zazhil998,21(4):221-223
[22]American Thoracic Society.Idiopathic pulmonary fibrosis:diagnosisandtreatment.Internationalconsensus statemen.American Thoracic Society(ATS),and the European Respiratory Society(ERS)[J].A mJ R espir Crit Care Med,2000,161(2 Pt):646-664
[23]Wang R,Ibarra-Sunga 0,Verlinski L,et al.Abrogation of bleomycin-induced epithelial apoptosis and lung fibrosis by captopril or by a caspase inhibitor.Am J Physiol Lung Cell Mol Physiol.2000;279(1):L143-151
[24]Robert J,Mason,Marvin Ⅰ,et al.Pharmacological therapy for idiopathic pulmonary fibrosis.Am J Respir Crit Card Med.1999;160(5pt 1):1771-1777
[25]李京红,何冰,翁保迎.转化生长因子-β1单克隆抗体对大鼠肺纤维化的治疗观察.中华结核和呼吸杂志.1997;20(6):347-349
[26]LossosIS,Breuer R,Shriki M,et al.Peribronchial lymphocyte activation,in lung injury.LifeSci.1998;63(13):1183-1193.
[27]Sciavolino PJ,Lee TH,Vilcek J.Interferon-beta induces metalloproteinase mRNA expression in human fibroblasts.Role of activator protein-1.J Biol Chem.1994;269(34):21627-21634
[28]王海涛,刘吴,颜京霞,等.N-乙酰-L-半胱氨酸对染矽尘大鼠肺间质成纤维细胞INF-Γ表达的影响.第三军医大学学报,2005,27(19):2003
[29]王海涛,高俊玲,田艳霞,等.N-乙酰-L-半胱氨酸对矽肺模型大鼠肺泡巨噬细胞基质金属蛋白酶2、9表达的影响.中华结核和呼吸杂志,2006,29(1):63-64