吸入性皮质类固醇激素对变应性鼻炎鼻黏膜病理改变影响的实验研究
|
摘要
目的:通过建立变应性鼻炎鼠类实验动物模型,探讨吸入性皮质类固醇激素对变应性鼻炎鼻黏膜重塑的影响。
方法:选健康SD大鼠300只,随机分成正常对照组A和实验组,A组60只,实验组240只。首先对实验组大鼠予以卵清白蛋白进行基础致敏、致敏加强、局部激发建立变应性鼻炎动物模型,A组正常对照组则以等量生理盐水代替进行腹腔注射及滴鼻。然后将实验组动物随机分为B、C、D、E四组,每组60只。分组后,对A组继续予以等量生理盐水每周两次滴鼻;B组不再予以任何刺激及治疗;C组不再予以OVA刺激,每天予以丙酸氟替卡松每侧鼻腔50μl/次喷鼻; D组继续予以等浓度等量OVA双侧鼻腔滴鼻,每周两次;E组继续予以等浓度等量OVA双侧鼻腔滴鼻每周两次的同时,每天予以丙酸氟替卡松每侧鼻腔50μl/次喷鼻。分别于治疗后第1、2、4、8、12、及16周末各从A、B、C、D、E组中随机挑选10只进行处死。从各组的10只大鼠中随机挑选一只行鼻黏膜微血管铸型,其余9只取鼻黏膜分别送病理检查、PCR及透射电镜检查,以观察鼻黏膜形态学改变、微血管铸型情况及TGF-β1、FGF-2表达情况。
结果:实验组大鼠动物模型建立成功,均表现出明显的抓鼻、喷嚏及流涕等症状。在接受变应原激发后鼻黏膜发生重塑改变,光镜下见鼻黏膜出现上皮剥脱,但尚未到基底层;并存在上皮杯状细胞化生,黏膜固有层出现腺体及血管增多,腺管增粗,炎症细胞浸润明显;电镜示上皮层纤毛不同程度脱落,排列欠整齐,基底膜板层网状结构增厚,可见胶原沉积及纤维增生,血管周围不同程度炎性细胞浸润,细胞明显水肿,组织间隙水肿也明显,但细胞间的结构尚未破坏;黏微血管明显增多,迂曲,分叉,粗细不一,微血管密度增加,并交织成网状;TGF-β1、FGF-2免疫阳性表达明显增高,TGF-β1mRNA表达升高。B组由于避免了变应原的接触,至第八周时,开始出现黏膜上皮剥脱减轻,至第十六周时黏膜上皮损伤情况才减轻较明显,炎症细胞浸润减少。TGF-β1、FGF-2免疫阳性表达及TGF-β1mRNA表达在第八周时开始下降。予以激素治疗后,C组在第八周上皮剥脱程度减轻,炎症细胞浸润减少,微血管相对减少,在第十六周鼻黏膜上皮层基本完整,腺样化生减轻,炎症细胞浸润不明显。而TGF-β1、FGF-2免疫阳性表达及TGF-β1mRNA表达在第四周时开始下降,至第十六周时已下降接近正常对照组水平。D组由于持续变应原接触,重塑进一步加重,TGF-β1、FGF-2免疫阳性表达及TGF-β1mRNA表达持续高水平。E组形态学改变无明显变化,至第十六周时仍可见到上皮杯状细胞化生明显,并可见大量黏液样物沉积于其中,黏膜下血管增粗。而TGF-β1、FGF-2免疫阳性表达及TGF-β1mRNA表达在第八周时开始下降,至第十六周时与C组比较无统计学差异。
结论:1以卵清白蛋白为变应原,可通过大SD大鼠成功建立稳定的变应性鼻炎实验动物模型。2变应性鼻炎鼻黏膜可发生黏膜重塑现象,在避免变应原的持续接触后,其症状可缓解,鼻黏膜的重塑可自行减轻;如果变应原持续接触,其重塑将进一步加重并呈现不可逆性改变。3在能够避免变应原接触的前提下,皮质类固醇激素可较好的控制变应性鼻炎的症状,并在一定程度逆转重塑,起到一定的治疗作用;而在变应原持续接触的情况下,皮质类固醇激素虽可控制症状,但并不能在短期内完全逆转鼻黏膜的重塑,对已经发生了不可逆性改变的黏膜结构并无逆转或明显修复作用。4变应性鼻炎鼻黏膜中TGF-β1、FGF-2等生长因子可出现高表达,而皮质类固醇激素可以下调TGF-β1、FGF-2等生长因子的表达水平,这可能是皮质类固醇激素治疗变应性鼻炎机理之一。5对于变应性鼻炎的治疗,避免变应原的接触仍是首选方法,辅以皮质类固醇激素治疗可起到较好的疗效。
Objective: To investigate the influence of the inhaled corticosteroids to the remodeling of the nasal mucosa in the allergic rhinitis, by establishing the allergic rhinitis model of the rats, which induced by OVA.
Methods: 300 Sprague-Dawley(SD) rats are selected and randomly divided into two groups: the normal Group A used for control and the experimental group. The number of the rats in Group A is 60 and the experiment group is 240.First of all, make the rats in experimental group be allergic with ovalbumin(OVA) and enhance it and do local stimulation in order to establish the animal model of allergic rhinitis. While do intra-peritoneal injection with physiological saline in the same volume as that of ovalbumin(OVA) in the experimental group and intranasal dropping on the rats in normal Group A. Next, the rats in experimental group are randomly divided into four groups, i.e. Group B, Group C, Group D, Group E. The number of rats in each group is 60.Randomly select 10 rats to kill from each groups respectively at the end of the first, second, fourth, eighth, twelfth and sixteenth week after treatment. Randomly select one from that ten rats in each group for micro-vascular casting of nasal mucosa, and the remaining nine are to get pathological examination, PCR and transmission electron microscope in order that I can observe the morphological changes, the micro-vascular casts and the expression of TGF-β1,FGF-2 in the nasal mucosa. And then, the rats in Group A get the intranasal dropping with physiologic saline in the same volume twice a week; rats in Group B are under no stimulation or treatment; rats in the Group C are no longer stimulated with OVA, but they are going to have fluticasone propionate(FP) nasal spray, each side 50μl /per day; rats in Group D still get the intranasal dropping on each side with OVA in the same volume and concentration twice a week; rats in Group E also get the intranasal dropping on each side with OVA in the same volume and concentration twice a week, moreover, they get FP nasal spray, each side 50μl /per day.
Results: The model on the rats in experimental group is established successfully: all the rats in the experimental groups show obvious symptoms: grasping noses, sneezing and running nose. After allergen stimulation, the nasal mucosa showed remodeling changes such as epithelial denudation, but it does not occur to the bottom and inflammatory cells infiltration becomes obvious with the help of optical microscope. And there are metaplasia of the goblet cells in epithelia and the number of gland and blood vessels increase in the mucosal layer and glandular vessels become thick. Cilia of epithelial shed to different extent and are uneven under the electron microscope, and the layers of reticular formation of basal membrane become thick, and collagen deposition and fabric hyperplasia are seen. There is inflammatory cells infiltration of different degrees around the blood vessels and edema in cells. Edemas in tissue spaces are also obvious and the structures between cells are not destroyed. And the micro-vascular in mucosa increase apparently. They are tortuous, branching, thick and thin. Density of blood capillary is increased and blood capillary becomes netted. The positive expression of immunohistochemistry of TGF-β1, FGF-2 rise obviously, in the meantime, TGF-β1 mRNA expression rises as well. Because of avoiding the exposure of allergen, epithelial denudations of mucosa in Group B are reducing from the eighth week. Till the sixteenth week, epithelial damage of the mucosa and inflammatory cells infiltration reduced obviously. TGF-β1、FGF-2 positive expression of immunity and TGF-β1m RNA expression drop in the eighth week. Under the treatment with corticosteroids, the degree of epithelial denudations and inflammatory cells infiltration of the rats in Group C are reduced, and micro-vascular are lessened in the eighth week. In the sixteenth week, epithelia of nasal mucosa are basically complete, glandular metaplasia alleviates, inflammatory cells infiltration become unobvious. The positive expression of immunohistochemistry of TGF-β1, FGF-2 and TGF-β1 mRNA expression decline in the fourth week, however, in the sixteenth week they draw close to the normal groups’. The positive expression of immunohistochemistry of TGF-β1, FGF-2 and TGF-β1 mRNA expression last high in Group D due to the continuously contact with allergen and enhancing remodeling. There are no obvious changes in morphology of the rats in Group E. Even in the sixteenth week, metaplasias of the goblet cells in epithelia are clear to be seen. Besides, a lot of mucus deposits in goblet cell, micro-vascular under the mucosa become thick. The positive expression of immunohistochemistry of TGF-β1, FGF-2 and TGF-β1 mRNA expression decline in the eighth week. Compared with Group C there is no differences in statistics in the sixteenth week.
Conclusion: 1. The animal model of the allergic rhinitis can be established on the SD rats using the ovalbumin as the allergen. 2. The remodeling of the nasal mucosa can be found in allergic rhinitis. If allergen can be avoided, the symptoms can be alleviated and the remodeling will reduce by itself; if the allergen are continuously contacted, the remodeling will aggravate. 3. Corticosteroids can control the symptoms of the allergic rhinitis better and reverse the remodeling to some extent and perform the therapeutical effects. While if allergen can not be avoided, although the symptoms can be controlled with corticosteroids somehow, it is impossible to reverse the remodeling completely in a short time. And it cannot retro-converse or repair the nasal mucosa while the irreversibile change has occurred. 4. Growth factors such as TGF-β1, FGF-2 express obviously in the mucosa in allergic rhinitis, and the expression could be lowed down by corticosteroids, maybe that’s one of the mechanisms of the corticosteroids to cure the AR. 5. Avoid allergen is still the preferred approach for the treatment of the allergic rhinitis. If we can make sure to avoid allergen, the therapy supplemented by corticosteroid is one of good choice.
方法:选健康SD大鼠300只,随机分成正常对照组A和实验组,A组60只,实验组240只。首先对实验组大鼠予以卵清白蛋白进行基础致敏、致敏加强、局部激发建立变应性鼻炎动物模型,A组正常对照组则以等量生理盐水代替进行腹腔注射及滴鼻。然后将实验组动物随机分为B、C、D、E四组,每组60只。分组后,对A组继续予以等量生理盐水每周两次滴鼻;B组不再予以任何刺激及治疗;C组不再予以OVA刺激,每天予以丙酸氟替卡松每侧鼻腔50μl/次喷鼻; D组继续予以等浓度等量OVA双侧鼻腔滴鼻,每周两次;E组继续予以等浓度等量OVA双侧鼻腔滴鼻每周两次的同时,每天予以丙酸氟替卡松每侧鼻腔50μl/次喷鼻。分别于治疗后第1、2、4、8、12、及16周末各从A、B、C、D、E组中随机挑选10只进行处死。从各组的10只大鼠中随机挑选一只行鼻黏膜微血管铸型,其余9只取鼻黏膜分别送病理检查、PCR及透射电镜检查,以观察鼻黏膜形态学改变、微血管铸型情况及TGF-β1、FGF-2表达情况。
结果:实验组大鼠动物模型建立成功,均表现出明显的抓鼻、喷嚏及流涕等症状。在接受变应原激发后鼻黏膜发生重塑改变,光镜下见鼻黏膜出现上皮剥脱,但尚未到基底层;并存在上皮杯状细胞化生,黏膜固有层出现腺体及血管增多,腺管增粗,炎症细胞浸润明显;电镜示上皮层纤毛不同程度脱落,排列欠整齐,基底膜板层网状结构增厚,可见胶原沉积及纤维增生,血管周围不同程度炎性细胞浸润,细胞明显水肿,组织间隙水肿也明显,但细胞间的结构尚未破坏;黏微血管明显增多,迂曲,分叉,粗细不一,微血管密度增加,并交织成网状;TGF-β1、FGF-2免疫阳性表达明显增高,TGF-β1mRNA表达升高。B组由于避免了变应原的接触,至第八周时,开始出现黏膜上皮剥脱减轻,至第十六周时黏膜上皮损伤情况才减轻较明显,炎症细胞浸润减少。TGF-β1、FGF-2免疫阳性表达及TGF-β1mRNA表达在第八周时开始下降。予以激素治疗后,C组在第八周上皮剥脱程度减轻,炎症细胞浸润减少,微血管相对减少,在第十六周鼻黏膜上皮层基本完整,腺样化生减轻,炎症细胞浸润不明显。而TGF-β1、FGF-2免疫阳性表达及TGF-β1mRNA表达在第四周时开始下降,至第十六周时已下降接近正常对照组水平。D组由于持续变应原接触,重塑进一步加重,TGF-β1、FGF-2免疫阳性表达及TGF-β1mRNA表达持续高水平。E组形态学改变无明显变化,至第十六周时仍可见到上皮杯状细胞化生明显,并可见大量黏液样物沉积于其中,黏膜下血管增粗。而TGF-β1、FGF-2免疫阳性表达及TGF-β1mRNA表达在第八周时开始下降,至第十六周时与C组比较无统计学差异。
结论:1以卵清白蛋白为变应原,可通过大SD大鼠成功建立稳定的变应性鼻炎实验动物模型。2变应性鼻炎鼻黏膜可发生黏膜重塑现象,在避免变应原的持续接触后,其症状可缓解,鼻黏膜的重塑可自行减轻;如果变应原持续接触,其重塑将进一步加重并呈现不可逆性改变。3在能够避免变应原接触的前提下,皮质类固醇激素可较好的控制变应性鼻炎的症状,并在一定程度逆转重塑,起到一定的治疗作用;而在变应原持续接触的情况下,皮质类固醇激素虽可控制症状,但并不能在短期内完全逆转鼻黏膜的重塑,对已经发生了不可逆性改变的黏膜结构并无逆转或明显修复作用。4变应性鼻炎鼻黏膜中TGF-β1、FGF-2等生长因子可出现高表达,而皮质类固醇激素可以下调TGF-β1、FGF-2等生长因子的表达水平,这可能是皮质类固醇激素治疗变应性鼻炎机理之一。5对于变应性鼻炎的治疗,避免变应原的接触仍是首选方法,辅以皮质类固醇激素治疗可起到较好的疗效。
Objective: To investigate the influence of the inhaled corticosteroids to the remodeling of the nasal mucosa in the allergic rhinitis, by establishing the allergic rhinitis model of the rats, which induced by OVA.
Methods: 300 Sprague-Dawley(SD) rats are selected and randomly divided into two groups: the normal Group A used for control and the experimental group. The number of the rats in Group A is 60 and the experiment group is 240.First of all, make the rats in experimental group be allergic with ovalbumin(OVA) and enhance it and do local stimulation in order to establish the animal model of allergic rhinitis. While do intra-peritoneal injection with physiological saline in the same volume as that of ovalbumin(OVA) in the experimental group and intranasal dropping on the rats in normal Group A. Next, the rats in experimental group are randomly divided into four groups, i.e. Group B, Group C, Group D, Group E. The number of rats in each group is 60.Randomly select 10 rats to kill from each groups respectively at the end of the first, second, fourth, eighth, twelfth and sixteenth week after treatment. Randomly select one from that ten rats in each group for micro-vascular casting of nasal mucosa, and the remaining nine are to get pathological examination, PCR and transmission electron microscope in order that I can observe the morphological changes, the micro-vascular casts and the expression of TGF-β1,FGF-2 in the nasal mucosa. And then, the rats in Group A get the intranasal dropping with physiologic saline in the same volume twice a week; rats in Group B are under no stimulation or treatment; rats in the Group C are no longer stimulated with OVA, but they are going to have fluticasone propionate(FP) nasal spray, each side 50μl /per day; rats in Group D still get the intranasal dropping on each side with OVA in the same volume and concentration twice a week; rats in Group E also get the intranasal dropping on each side with OVA in the same volume and concentration twice a week, moreover, they get FP nasal spray, each side 50μl /per day.
Results: The model on the rats in experimental group is established successfully: all the rats in the experimental groups show obvious symptoms: grasping noses, sneezing and running nose. After allergen stimulation, the nasal mucosa showed remodeling changes such as epithelial denudation, but it does not occur to the bottom and inflammatory cells infiltration becomes obvious with the help of optical microscope. And there are metaplasia of the goblet cells in epithelia and the number of gland and blood vessels increase in the mucosal layer and glandular vessels become thick. Cilia of epithelial shed to different extent and are uneven under the electron microscope, and the layers of reticular formation of basal membrane become thick, and collagen deposition and fabric hyperplasia are seen. There is inflammatory cells infiltration of different degrees around the blood vessels and edema in cells. Edemas in tissue spaces are also obvious and the structures between cells are not destroyed. And the micro-vascular in mucosa increase apparently. They are tortuous, branching, thick and thin. Density of blood capillary is increased and blood capillary becomes netted. The positive expression of immunohistochemistry of TGF-β1, FGF-2 rise obviously, in the meantime, TGF-β1 mRNA expression rises as well. Because of avoiding the exposure of allergen, epithelial denudations of mucosa in Group B are reducing from the eighth week. Till the sixteenth week, epithelial damage of the mucosa and inflammatory cells infiltration reduced obviously. TGF-β1、FGF-2 positive expression of immunity and TGF-β1m RNA expression drop in the eighth week. Under the treatment with corticosteroids, the degree of epithelial denudations and inflammatory cells infiltration of the rats in Group C are reduced, and micro-vascular are lessened in the eighth week. In the sixteenth week, epithelia of nasal mucosa are basically complete, glandular metaplasia alleviates, inflammatory cells infiltration become unobvious. The positive expression of immunohistochemistry of TGF-β1, FGF-2 and TGF-β1 mRNA expression decline in the fourth week, however, in the sixteenth week they draw close to the normal groups’. The positive expression of immunohistochemistry of TGF-β1, FGF-2 and TGF-β1 mRNA expression last high in Group D due to the continuously contact with allergen and enhancing remodeling. There are no obvious changes in morphology of the rats in Group E. Even in the sixteenth week, metaplasias of the goblet cells in epithelia are clear to be seen. Besides, a lot of mucus deposits in goblet cell, micro-vascular under the mucosa become thick. The positive expression of immunohistochemistry of TGF-β1, FGF-2 and TGF-β1 mRNA expression decline in the eighth week. Compared with Group C there is no differences in statistics in the sixteenth week.
Conclusion: 1. The animal model of the allergic rhinitis can be established on the SD rats using the ovalbumin as the allergen. 2. The remodeling of the nasal mucosa can be found in allergic rhinitis. If allergen can be avoided, the symptoms can be alleviated and the remodeling will reduce by itself; if the allergen are continuously contacted, the remodeling will aggravate. 3. Corticosteroids can control the symptoms of the allergic rhinitis better and reverse the remodeling to some extent and perform the therapeutical effects. While if allergen can not be avoided, although the symptoms can be controlled with corticosteroids somehow, it is impossible to reverse the remodeling completely in a short time. And it cannot retro-converse or repair the nasal mucosa while the irreversibile change has occurred. 4. Growth factors such as TGF-β1, FGF-2 express obviously in the mucosa in allergic rhinitis, and the expression could be lowed down by corticosteroids, maybe that’s one of the mechanisms of the corticosteroids to cure the AR. 5. Avoid allergen is still the preferred approach for the treatment of the allergic rhinitis. If we can make sure to avoid allergen, the therapy supplemented by corticosteroid is one of good choice.
引文
[1] Sadeq AQ,Michael JD,TimothyJC.Inflammatory Responses in Allergic Rhinitis:Traditional Approaches and Novel Treatment Strategies. J Am Osteopath Assoc.2004;104(5):7S -15S.
[2] 佘文煜,董震.实验性变应性鼻炎鼻黏膜组织重塑的特点.中华耳鼻咽喉头颈外科杂志.2006;41:48-53.
[3] Bousquet J,Jacot W,Vignola AM,et al.Allergic rhinitis:a disease remodeling the upper airways? J Allergy Clin Immunol. 2004;113(1):43-9.
[4] Bousquet J,Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol.2001.108(Supp15):147-334.
[5] Holm AF, Fokkens WJ. Topical corticosteroids in allergic rhinitis; effects on nasal inflammatory cells and nasal mucosa. Clinical & Experimental Allergy. 2001;529.
[6] 赵秀杰,董震,杨占泉,等.鼻超敏反应实验模型的建立.中华耳鼻咽喉科杂志.1993;28(1):17-18.
[7] Schneider T,Van-Velzen D,Moqbel R, et al. Kinetics and quantitation of eosinophil and neutrophil recruitment to allergic lung inflammation in a brown Norway rat model[J]. Am J Respir Cell Mol Biol, 1997, 17(6): 702-712.
[8] 安云芳,赵长青,朱庆义,等. 变应性鼻炎鼻粘膜P物质受体的研究. 中华耳鼻咽喉科杂志,1998,33(3):139～142.
[9] Hylkema MN, Timens W, Luinge M, Van Der WN, Hoekstra MO. The effect of bacillus Calmette-Guerin immunization depends on the genetic predisposition to Th2-type responsiveness. Am J Respir Cell Mol Bio.2002;27:244–249.
[10] 王向东,韩德民,周兵,等.白细胞介素5调节变应性鼻炎骨髓反应的实验研究.中华耳鼻咽喉科杂志,2003,38(6):448-450.
[11] Sonoyama, K., Watanabe, H., Watanabe, J,et,al. Allergic airway eosinophilia is suppressed in ovalbumin-sensitized Brown Norway rats fed raffinose and α-linked galactooligosaccharide. Journal of Nutrition.2005;135(3):538-543.
[12] 周明辉,董明敏,吴玉瑛,等. Eotaxin 基因和趋化因子受体3在变应性鼻炎大鼠模型鼻腔黏膜和骨髓中的表达及意义.临床耳鼻咽喉科杂志,2006,20(5):227-230.
[13] Shimizu T,Hirano H,Majima Y,et al.A Mechanism of Antigen-induced Mucus Production in Nasal Epithelium of Sensitized Rats. Am J Respir Crit Care Med.2000; 161 (5):1648-1654.
[14] El-Sakka AI, Lin CS, Chui RM, et al. Effects of diabetes on nitric oxide synthase and growth factor genes and protein expression in an animal model. Int J Impot Res. 1999;11:123–132.
[15] Rajasekaran M, Kasyan A,Jain A, et al. Altered growth factor expression in the aging penis: the Brown-Norway rat model J Androl, May 1, 2002; 23(3): 393 - 399.
[16] 邱录斌,刘月辉.豚鼠鼻黏膜微血管铸型的制作..解剖学研究.2005;27(2):152-153
[17] 吴坤成,李泽宇,刘畅,等.脑血管铸型标本的设计与制作.解剖学杂志.2005;28(6):643-649.
[18] Tingsgaard PK,Larsen PL,Bock T,et al. Expression of intercellular adhesion molecule - 1 on the vascular endothelium in nasal polyps before,during and after topical glucocorticoid treatment[J].Acta Otolaryngol Stockh ,1998,118:404 - 408.
[19] Kliem V,Johnson RJ,Alpers CE,et al.Mechanism involved in the pathogenesis of tubulointerstital fibrosis in 5/6-nephrectomized rats.Kidney Int.1996;49:666-678.
[20] 赵宇,C Andrew van Hasselt,吴港生,等.卵白蛋白经鼻致敏建立变应性鼻炎动物模型.中华耳鼻咽喉头颈外科杂志.2005;40(3):176-180.
[21] Tanaka K, Okamoto Y, Nagaya Y, et al1 A nasal allergy model developed in the guinea p ig by intranasal app lication of 2, 4-to luenediisocyanate. Int Arch Allergy Appl Immunol. 1988; 85:392.
[22] 张范英,韩德民,诸小侬,等.辣椒辣素治疗试验性变应性鼻炎的组织病理学及免疫组织化学研究.中华耳鼻咽喉科杂志.1999;34:229-231.
[23] 赵秀杰,董震,杨占泉,等.鼻超敏反应实验模型的建立.中华耳鼻咽喉科杂志,.1993; 28: 172-181.
[24] Asakura K,Saito H,Kataura A.In vivo effects of monoclonal antibody against ICAM-1 and LFA-1 on antigen-induced nasal symp toms and eosinophilia in sensitized rats.Int Arch Allergy Immunol.1996;111: 156-160.
[25] Shimizu T, Hirano H, Majima Y, et al.A mechanism of antigen-induced mucus production in nasal epithelium of sensitized rats. Am J Resp ir Crit CareMed.2000;161: 1648-1654.
[26] van de Rijin M, Mehlhop PD, Judkins A, et al.A murine model of allergic rhinitis: studies on the role of IgE in pathogenesis and analysis of eosinophil influx elicited by allergen and eotaxin. J Allergy Clin Immunol.1998;102: 65-74.
[27] Nabe T, Shimizu K, MizutaniN, et al1 A new model of experimental allergic rhinitis using Japanese cedar pollen in guinea p igs.Jpn J Pharmacol.1997; 75: 243-251.
[28] Nabe T,Mizutani N,Shimizu K,et al.Development of pollen induced allergic rhinitis with early and late phase nasal blockage in guinea pigs.Inflamm Res.1998;47(9):369-374.
[29] Farraj AK,Harkema JR,Kaminski NE,et al.Allergic rhinitis induced by intranasal sensitization and challenge with trimellitic anhydride but not with dinitrochlorobenzene or oxazolone in A/J mice.Toxicol Sci.2004;79(2):325-325.
[30] 杨瑞嘉,黄志纯.变应性鼻炎动物模型的建立及评价.国际耳鼻咽喉头颈外科杂志.2007;31(2):87-89.
[31] Hunter DD,Satterfield BE,Huang J,et al.Toluene diisoeyanate enhances substance P in sensory neurons innervating the nasal mucosa.Am J Respi Crit Care Med.2000;161(2 Pt 1):543-549.
[32] Saito H,Howie K,Watie J,et al.Allergen-induced murine upper airway inflammation:local and systemic changes in murine experimental allergic rhinitis.Immunology.2001;104(2):226-234.
[33] Beckett PA,Howarth PH.Pharmacotherapy and airway remodeling in asthma?.Thorax 2003;58:163-174.
[34] Takeuchi K,Suzuki S,Majima Y.Morphological and functional changes of epithelial cells in allergic rhinitis. Clinical & Experimental Allergy Reviews.2006;6 (4):106–110.
[35] Watanabe K,Kiuna C.Epithelial damage of nasal mucosa in nasal allergic.Ann Otol RhinolLaryngol.1998;107:564-570.
[36] Nagata H,Motosugi H,Sanai A,et al.Enhancement of submicroscopic damage of the nasal epithelium by topical allergic challenge in patients with perennial nasal allergic. Ann Otol Rhinol Laryngol.2000;110:236-242.
[37] 梁乐,刘红刚,何春燕.慢性鼻-鼻窦炎增厚基底膜样物质的形态学研究.中华耳鼻咽喉头颈外科杂志.2006;41(1):31-34.
[38] Sanai A,Nagata H,Konno A.Extensive interstitial collagen deposition on the basement membrane zone in allergic nasal mucosa[J].Acta Otolaryngol.1999;119(4):473-478.
[39] 吉晓滨,柳息洪,臧林泉等.豚鼠变应性鼻炎模型鼻黏膜基底膜增最重塑的超微结构.中国耳鼻咽喉头颈外科杂志.2007;13(4):250-252.
[40] Peter J, Barnes D M, D Sc.Inhaled glucocorticoids for Asthma. The New England Journal of Medicine. 1995;332:868-875.
[41] Ciprandi G,Ricca V,Paola F,et al.Duration of antiinflammatory and symptomatic effects after suspension of intranasal corticosteroid in persistent allergic rhinitis.Eur Ann Allergy Clin Immunol. 2004;36(2):63-6.
[42] Storms W. Allergic rhinitis-induced nasal congestion: its impact on sleep quality. Prim Care Respir J.2008;17(2):7-18.
[43] Lanier BQ. Use of Intranasal Corticosteroids in the Management of Congestion and Sleep Disturbance in Pediatric Patients With Allergic Rhinitis. Clin Pediatr (Phila). 2008 Jan 11 [Epub ahead of print].
[44] John M W,Michael J A,Robert M P.Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis:systematic review of randomised controlled trial.BMJ 1998;317(12):1624-1629.
[45] Wenju Lu, Erik P. Lillehoj, et al.Effects of dexamethasone on Muc5ac mucin production by primary airway goblet cells.Am J Physiol Lung Cell Mol Physiol.2005;288: L52-L60.
[46] Marina Miller, Jae Youn Cho, Kirsti McElwain, Shauna McElwain, Jung Yeon Shim, Michael Manni, Ji Sun Baek, and David H Broide. Corticosteroids prevent myofibroblast accumulation and airway remodeling in mice. Am J Physiol Lung Cell Mol Physiol, Jan 2006; 290: L162-L169.
[47] Ward C, Pais M, Bish R, Reid D, Feltis B, Johns D, Walters EH. Airway inflammation, basement membrane thickening and bronchial hyperresponsiveness in asthma. Thorax 2002;57:309–316.
[48] Wilson AM, Orr LC, Sims EJ, Dempsey OJ, and Lipworth BJ. Antiasthmatic Effects of Mediator Blockade versus Topical Corticosteroids in Allergic Rhinitis and Asthma. Am. J. Respir. Crit. Care Med., 2000;162: 1297-1301.
[49] 张罗,周兵,韩德民等。变应性鼻炎研究进展(三):鼻用皮质类固醇的药理作用。中国耳鼻咽喉头颈外科。2004;11:67-72
[50] Pascal Chanez, Arnaud Bourdin, Isabelle Vachier, Philippe Godard, Jean Bousquet and A. M. Vignola. Effects of Inhaled Corticosteroids on Pathology in Asthma and Chronic Obstructive Pulmonary Disease. The Proceedings of the American Thoracic Society .2004;1:184-190.
[51] Grol MH,Gerritsen J,Vonk JM,et al.Risk factors for growth and decline of lung function inasthmatic individuals up to age 42 years.A 30-year follow-up study. Am J Respir Crit Care Med 1999;160:1830–7.
[52] Horvath G,Wanner A.Inhaled corticosteroids:effects on the airway vasculature in bronchial asthma.Eur Respir J.2006; 27:172-187.
[53] Robert J, Ho mer and Jack A, Elias. Airway remodeling in asthma: Therapeutic implications of mechanisms. Physiology.2005.20:28-35.
[54] Komai M,Tanaka H,Masuda T,et al.Role of Th2 responses in the development of allergen-induced airway remodeling in a murine model of allergic asthma. Brithish Journal of Pharmacology.2003,138(5):919-920.
[55] Redington AE,Roche WR,Holgate ST,et al.Co-localization of immunoreactive transforming growth factor-?1 and decorin in bronchial biopsies from asthmatic and normal subjects.J Pathol 1998;186:410–415.
[56] Blobe GC,Schiemann WP,Lodish HF.Role of transforming growth factor-? in human disease.N Engl J Med.2000;342:1350–1358.
[57] Nakamura T,Sakata R,Ueno T,et al.Inhibition of transforming growth factor beta prevents progression of liver fibrosis and enhances hepatocyte regeneration in dimethylnitrosamine-treated rats. Hepatology.2000;32:247–55.
[58] Kopp J, Factor V, Mozes M, et al. Transgenic mice with increased plasma levels of TGF-beta 1 develop progressive renal disease. Lab Invest.1996;74:991–1003.
[59] Giri S,Hyde D,Hollinger M.Effect of antibody to transforming growth factor ? on bleomycin induced accumulation of lung collagen in mice. Thorax.1993;48:959–66.
[60] Broekelman T,Limper A,Colby T, et al. Transforming growth factor beta-1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis.Proc Natl Acad Sci USA.1991;88:6642–6.
[61] Zhang H,Phan S.Inhibition of myofibroblast apoptosis by transforming growth factor ?1. Am J Respir Cell Mol Bio.1999;21:658–65.)
[62] Kenyon NJ, Ward RW, Grew GM,et al.TGF-?1 causes airway fibrosis and increased collagen I and III mRNA in mice. Thorax.2003;58:772-777.)
[63] Lee, SS, Won, TB,Kim, JW,et al. Effects of Dexamethasone on the Expression of Transforming Growth Factor-[beta] in the Mouse Model of Allergic Rhinitis. Laryngoscope. 2007;117(8):1323-1328.
[64] 于睿莉,朱冬冬,董震.中华耳鼻咽喉头颈外科杂志.2006;41(10):773-776.
[65] Kranenburg AR. Willems-Widyastuti A. Mooi WJ,et al.Chronic obstructive pulmonary disease is associated with enhanced bronchial expression of FGF-1,FGF-2,and FGFR-1.Journal of Pathology.2005;206(1):28-38.
[66] Shute JK,Solic N,Shimizu J,et al.Epithelial expression and release of FGF-2 from heparan sulphate binding sites in bronchial tissue in asthma.Thorax.2004,;59: 557-562.
1. 佘文煜,董震。实验性变应性鼻炎鼻黏膜组织重塑的特点。中华耳鼻咽喉头颈外科杂志,2006,41:48—53。
2. Bousquet J, Jacot W, Vignola AM, Bachert C, Van Cauwenberge P. Allergic rhinitis: a disease remodeling the upper airways? J Allergy Clin Immunol. 2004 Jan;113(1):43-9.
3. Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med 2000;161:1720-45.
4. P A Beckett, P H Howarth. Pharmacotherapy and airway remodeling in asthma?.Thorax 2003;58:163-174.
5. Bousquet J, Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol.2001.108(Supp15):147-334.
6. Komai M, Tanaka H, Masuda T, Nagao K, Ishizaki M, Sawada M, Nagai H. Role of Th2 responses in the development of allergen-induced airway remodeling in a murine model of allergic asthma. Brithish Journal of Pharmacology.2003,138(5):919-920.
7. Robert J, Ho mer and Jack A, Elias. Airway remodeling in asthma: Therapeutic implications ofmechanisms. Physiology,2005.20:28-35.
8. Vignola AM, Chanez P, Chiappara G, et al. Transforming growth factor-? expression in mucosal biopsies in asthma and chronic bronchitis. Am J Respir Crit Care Med 1997;160:1001–8.
9. Redington A, Madden J, Frew A, et al. Transforming growth factor ?1 in asthma: measurement in bronchoalveolar lavage fluid. Am J Respir Crit Care Med 1997;156:642–7.
10. N J Kenyon, R W Ward, G McGrew and J A Last. TGF-?1 causes airway fibrosis and increased collagen I and III mRNA in mice. Thorax 2003;58:772-777.
11. Hu Peng,Abha Sahni,Philip Fay,et al. Identification of a binding site on human FGF-2 for fibrinogen. Blood,2004;103(6), pp. 2114-2120
12. Ynuk Bosse, Charles Thompson, Jana Stankova, and Marek Rola-Pleszczynski. FGF-2 and TGF-β1 Synergism in Human bronchial smooth muscle cell proliferation.Am.J.Respir.Cell Mol.Biol. Jan 2006;10,1165/rcmb.2005-0309oc.
13. Ward C, Walters H. Airway wall remodeling: the influence of corticosteroids. Current Opinion in Allergy & Clinical Immunology.2005;5(1):43-48.
14. Ann Hoeben, Bart Landuyt, Martin S, Highley, Hans Wildiers, Allan T. Van Osterom and Ernst A. De Bruijn. Vascular Endothelial growth factor and angiogenesis. Pharmacol Rev 2004; 56: 549-580.
15. Weiner JM, Abramson JM, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomized controlled trials. BMJ 1998;317:1624-1629.
16. Peter J, Barnes D M, D Sc. Inhaled glucocorticoids for Asthma. The New England Journal of Medicine. 1995;332:868-875.
17. Pascal Chanez, Arnaud Bourdin, Isabelle Vachier, Philippe Godard, Jean Bousquet and A. M. Vignola. Effects of Inhaled Corticosteroids on Pathology in Asthma and Chronic Obstructive Pulmonary Disease. The Proceedings of the American Thoracic Society .2004;1:184-190.
18. Boulet LP, Turcotte H, Laviolette M, Naud F, Bernier MC, Martel S, Chakir J. Airway hyperresponsiveness, inflammation, and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma: influence of inhaled corticosteroids. Am J Respir Crit Care Med 2000;162:1308–1313.
19. Ward C, Pais M, Bish R, Reid D, Feltis B, Johns D, Walters EH. Airway inflammation, basement membrane thickening and bronchial hyperresponsiveness in asthma. Thorax 2002;57:309–316.
20. Grol MH, Gerritsen J, Vonk JM, et al. Risk factors for growth and decline of lung function in asthmatic individuals up to age 42 years. A 30-year follow-up study. Am J Respir Crit Care Med 1999;160:1830–7.
21. Marina Miller, Jae Youn Cho, Kirsti McElwain, Shauna McElwain, Jung Yeon Shim, Michael Manni, Ji Sun Baek, and David H Broide. Corticosteroids prevent myofibroblast accumulation and airway remodeling in mice. Am J Physiol Lung Cell Mol Physiol, Jan 2006; 290: L162-L169.
22. Laitinen A, Altraja A, Kampe M, Linden M, Virtanen I, Laitinen LA. Tenascin is increased in airway basement membrane of asthmatics and decreased by an inhaled steroid. Am J Respir CritCare Med 1997;156:951–958.
23. Darren Fernandes, Elizabeth Guida, Valentina Koutsoubos, Trudi Harris, Peter Vadiveloo, John W. Wilson, and Alastair G. Stewart. Glucocorticoids Inhibit Proliferation, Cyclin D1 Expression, and Retinoblastoma Protein Phosphorylation, but Not Activity of the Extracellular-Regulated Kinases in Human Cultured Airway Smooth Muscle. Am.J.Respir.Cell Mol.Biol. 1999; 21(1): 77-88.
24. Wenju Lu, Erik P. Lillehoj, and K. Chul Kim. Effects of dexamethasone on Muc5ac mucin production by primary airway goblet cells. Am J Physiol Lung Cell Mol Physiol 2005;288: L52-L60.
25. G Horvath and A Wanner. Inhaled corticosteroids: effects on the airway vasculature in bronchial asthma. Eur Respir J 2006; 27:172-187.
26. Bernadette E Orsida, Xun Li, Bernadette Hickey, Frank Thien, John W Wilson, E Haydn Walters. Vascularity in asthmatic airways: relation to inhaled steroid dose. Thorax 1999;54:289-295
27. Wignarajah D, Zheng L,Harding R,et al. Inhaled corticosteroids and VEGF concentrations in asthmatic bronchoalveolar lavage fluid.Thorax 2003;58(Suppl3):15.
28. McCormack, Paul L, Plosker, Greg L. Inhaled mometasone furoate: a review of its use in persistent asthma in adults and adolescents. Adis Drug Evaluation. 2006;volume66(8):pp 1151-1168.
29. 顾瑞金.糖皮质激素为中重度变应性鼻炎治疗的一线用药.中华耳鼻咽喉科杂志.2004;9:574-576.
30. Richards DH & Scadding GK. Inhaled and intranasal steroids: the differences explained in terms of potential for growth effects. Allergy 2000; 55:S252.
31. A. F. Holm and W. J. Fokkens. Topical corticosteroids in allergic rhinitis; effects on nasal inflammatory cells and nasal mucosa. Clinical & Experimental Allergy. 2001;529.
[2] 佘文煜,董震.实验性变应性鼻炎鼻黏膜组织重塑的特点.中华耳鼻咽喉头颈外科杂志.2006;41:48-53.
[3] Bousquet J,Jacot W,Vignola AM,et al.Allergic rhinitis:a disease remodeling the upper airways? J Allergy Clin Immunol. 2004;113(1):43-9.
[4] Bousquet J,Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol.2001.108(Supp15):147-334.
[5] Holm AF, Fokkens WJ. Topical corticosteroids in allergic rhinitis; effects on nasal inflammatory cells and nasal mucosa. Clinical & Experimental Allergy. 2001;529.
[6] 赵秀杰,董震,杨占泉,等.鼻超敏反应实验模型的建立.中华耳鼻咽喉科杂志.1993;28(1):17-18.
[7] Schneider T,Van-Velzen D,Moqbel R, et al. Kinetics and quantitation of eosinophil and neutrophil recruitment to allergic lung inflammation in a brown Norway rat model[J]. Am J Respir Cell Mol Biol, 1997, 17(6): 702-712.
[8] 安云芳,赵长青,朱庆义,等. 变应性鼻炎鼻粘膜P物质受体的研究. 中华耳鼻咽喉科杂志,1998,33(3):139～142.
[9] Hylkema MN, Timens W, Luinge M, Van Der WN, Hoekstra MO. The effect of bacillus Calmette-Guerin immunization depends on the genetic predisposition to Th2-type responsiveness. Am J Respir Cell Mol Bio.2002;27:244–249.
[10] 王向东,韩德民,周兵,等.白细胞介素5调节变应性鼻炎骨髓反应的实验研究.中华耳鼻咽喉科杂志,2003,38(6):448-450.
[11] Sonoyama, K., Watanabe, H., Watanabe, J,et,al. Allergic airway eosinophilia is suppressed in ovalbumin-sensitized Brown Norway rats fed raffinose and α-linked galactooligosaccharide. Journal of Nutrition.2005;135(3):538-543.
[12] 周明辉,董明敏,吴玉瑛,等. Eotaxin 基因和趋化因子受体3在变应性鼻炎大鼠模型鼻腔黏膜和骨髓中的表达及意义.临床耳鼻咽喉科杂志,2006,20(5):227-230.
[13] Shimizu T,Hirano H,Majima Y,et al.A Mechanism of Antigen-induced Mucus Production in Nasal Epithelium of Sensitized Rats. Am J Respir Crit Care Med.2000; 161 (5):1648-1654.
[14] El-Sakka AI, Lin CS, Chui RM, et al. Effects of diabetes on nitric oxide synthase and growth factor genes and protein expression in an animal model. Int J Impot Res. 1999;11:123–132.
[15] Rajasekaran M, Kasyan A,Jain A, et al. Altered growth factor expression in the aging penis: the Brown-Norway rat model J Androl, May 1, 2002; 23(3): 393 - 399.
[16] 邱录斌,刘月辉.豚鼠鼻黏膜微血管铸型的制作..解剖学研究.2005;27(2):152-153
[17] 吴坤成,李泽宇,刘畅,等.脑血管铸型标本的设计与制作.解剖学杂志.2005;28(6):643-649.
[18] Tingsgaard PK,Larsen PL,Bock T,et al. Expression of intercellular adhesion molecule - 1 on the vascular endothelium in nasal polyps before,during and after topical glucocorticoid treatment[J].Acta Otolaryngol Stockh ,1998,118:404 - 408.
[19] Kliem V,Johnson RJ,Alpers CE,et al.Mechanism involved in the pathogenesis of tubulointerstital fibrosis in 5/6-nephrectomized rats.Kidney Int.1996;49:666-678.
[20] 赵宇,C Andrew van Hasselt,吴港生,等.卵白蛋白经鼻致敏建立变应性鼻炎动物模型.中华耳鼻咽喉头颈外科杂志.2005;40(3):176-180.
[21] Tanaka K, Okamoto Y, Nagaya Y, et al1 A nasal allergy model developed in the guinea p ig by intranasal app lication of 2, 4-to luenediisocyanate. Int Arch Allergy Appl Immunol. 1988; 85:392.
[22] 张范英,韩德民,诸小侬,等.辣椒辣素治疗试验性变应性鼻炎的组织病理学及免疫组织化学研究.中华耳鼻咽喉科杂志.1999;34:229-231.
[23] 赵秀杰,董震,杨占泉,等.鼻超敏反应实验模型的建立.中华耳鼻咽喉科杂志,.1993; 28: 172-181.
[24] Asakura K,Saito H,Kataura A.In vivo effects of monoclonal antibody against ICAM-1 and LFA-1 on antigen-induced nasal symp toms and eosinophilia in sensitized rats.Int Arch Allergy Immunol.1996;111: 156-160.
[25] Shimizu T, Hirano H, Majima Y, et al.A mechanism of antigen-induced mucus production in nasal epithelium of sensitized rats. Am J Resp ir Crit CareMed.2000;161: 1648-1654.
[26] van de Rijin M, Mehlhop PD, Judkins A, et al.A murine model of allergic rhinitis: studies on the role of IgE in pathogenesis and analysis of eosinophil influx elicited by allergen and eotaxin. J Allergy Clin Immunol.1998;102: 65-74.
[27] Nabe T, Shimizu K, MizutaniN, et al1 A new model of experimental allergic rhinitis using Japanese cedar pollen in guinea p igs.Jpn J Pharmacol.1997; 75: 243-251.
[28] Nabe T,Mizutani N,Shimizu K,et al.Development of pollen induced allergic rhinitis with early and late phase nasal blockage in guinea pigs.Inflamm Res.1998;47(9):369-374.
[29] Farraj AK,Harkema JR,Kaminski NE,et al.Allergic rhinitis induced by intranasal sensitization and challenge with trimellitic anhydride but not with dinitrochlorobenzene or oxazolone in A/J mice.Toxicol Sci.2004;79(2):325-325.
[30] 杨瑞嘉,黄志纯.变应性鼻炎动物模型的建立及评价.国际耳鼻咽喉头颈外科杂志.2007;31(2):87-89.
[31] Hunter DD,Satterfield BE,Huang J,et al.Toluene diisoeyanate enhances substance P in sensory neurons innervating the nasal mucosa.Am J Respi Crit Care Med.2000;161(2 Pt 1):543-549.
[32] Saito H,Howie K,Watie J,et al.Allergen-induced murine upper airway inflammation:local and systemic changes in murine experimental allergic rhinitis.Immunology.2001;104(2):226-234.
[33] Beckett PA,Howarth PH.Pharmacotherapy and airway remodeling in asthma?.Thorax 2003;58:163-174.
[34] Takeuchi K,Suzuki S,Majima Y.Morphological and functional changes of epithelial cells in allergic rhinitis. Clinical & Experimental Allergy Reviews.2006;6 (4):106–110.
[35] Watanabe K,Kiuna C.Epithelial damage of nasal mucosa in nasal allergic.Ann Otol RhinolLaryngol.1998;107:564-570.
[36] Nagata H,Motosugi H,Sanai A,et al.Enhancement of submicroscopic damage of the nasal epithelium by topical allergic challenge in patients with perennial nasal allergic. Ann Otol Rhinol Laryngol.2000;110:236-242.
[37] 梁乐,刘红刚,何春燕.慢性鼻-鼻窦炎增厚基底膜样物质的形态学研究.中华耳鼻咽喉头颈外科杂志.2006;41(1):31-34.
[38] Sanai A,Nagata H,Konno A.Extensive interstitial collagen deposition on the basement membrane zone in allergic nasal mucosa[J].Acta Otolaryngol.1999;119(4):473-478.
[39] 吉晓滨,柳息洪,臧林泉等.豚鼠变应性鼻炎模型鼻黏膜基底膜增最重塑的超微结构.中国耳鼻咽喉头颈外科杂志.2007;13(4):250-252.
[40] Peter J, Barnes D M, D Sc.Inhaled glucocorticoids for Asthma. The New England Journal of Medicine. 1995;332:868-875.
[41] Ciprandi G,Ricca V,Paola F,et al.Duration of antiinflammatory and symptomatic effects after suspension of intranasal corticosteroid in persistent allergic rhinitis.Eur Ann Allergy Clin Immunol. 2004;36(2):63-6.
[42] Storms W. Allergic rhinitis-induced nasal congestion: its impact on sleep quality. Prim Care Respir J.2008;17(2):7-18.
[43] Lanier BQ. Use of Intranasal Corticosteroids in the Management of Congestion and Sleep Disturbance in Pediatric Patients With Allergic Rhinitis. Clin Pediatr (Phila). 2008 Jan 11 [Epub ahead of print].
[44] John M W,Michael J A,Robert M P.Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis:systematic review of randomised controlled trial.BMJ 1998;317(12):1624-1629.
[45] Wenju Lu, Erik P. Lillehoj, et al.Effects of dexamethasone on Muc5ac mucin production by primary airway goblet cells.Am J Physiol Lung Cell Mol Physiol.2005;288: L52-L60.
[46] Marina Miller, Jae Youn Cho, Kirsti McElwain, Shauna McElwain, Jung Yeon Shim, Michael Manni, Ji Sun Baek, and David H Broide. Corticosteroids prevent myofibroblast accumulation and airway remodeling in mice. Am J Physiol Lung Cell Mol Physiol, Jan 2006; 290: L162-L169.
[47] Ward C, Pais M, Bish R, Reid D, Feltis B, Johns D, Walters EH. Airway inflammation, basement membrane thickening and bronchial hyperresponsiveness in asthma. Thorax 2002;57:309–316.
[48] Wilson AM, Orr LC, Sims EJ, Dempsey OJ, and Lipworth BJ. Antiasthmatic Effects of Mediator Blockade versus Topical Corticosteroids in Allergic Rhinitis and Asthma. Am. J. Respir. Crit. Care Med., 2000;162: 1297-1301.
[49] 张罗,周兵,韩德民等。变应性鼻炎研究进展(三):鼻用皮质类固醇的药理作用。中国耳鼻咽喉头颈外科。2004;11:67-72
[50] Pascal Chanez, Arnaud Bourdin, Isabelle Vachier, Philippe Godard, Jean Bousquet and A. M. Vignola. Effects of Inhaled Corticosteroids on Pathology in Asthma and Chronic Obstructive Pulmonary Disease. The Proceedings of the American Thoracic Society .2004;1:184-190.
[51] Grol MH,Gerritsen J,Vonk JM,et al.Risk factors for growth and decline of lung function inasthmatic individuals up to age 42 years.A 30-year follow-up study. Am J Respir Crit Care Med 1999;160:1830–7.
[52] Horvath G,Wanner A.Inhaled corticosteroids:effects on the airway vasculature in bronchial asthma.Eur Respir J.2006; 27:172-187.
[53] Robert J, Ho mer and Jack A, Elias. Airway remodeling in asthma: Therapeutic implications of mechanisms. Physiology.2005.20:28-35.
[54] Komai M,Tanaka H,Masuda T,et al.Role of Th2 responses in the development of allergen-induced airway remodeling in a murine model of allergic asthma. Brithish Journal of Pharmacology.2003,138(5):919-920.
[55] Redington AE,Roche WR,Holgate ST,et al.Co-localization of immunoreactive transforming growth factor-?1 and decorin in bronchial biopsies from asthmatic and normal subjects.J Pathol 1998;186:410–415.
[56] Blobe GC,Schiemann WP,Lodish HF.Role of transforming growth factor-? in human disease.N Engl J Med.2000;342:1350–1358.
[57] Nakamura T,Sakata R,Ueno T,et al.Inhibition of transforming growth factor beta prevents progression of liver fibrosis and enhances hepatocyte regeneration in dimethylnitrosamine-treated rats. Hepatology.2000;32:247–55.
[58] Kopp J, Factor V, Mozes M, et al. Transgenic mice with increased plasma levels of TGF-beta 1 develop progressive renal disease. Lab Invest.1996;74:991–1003.
[59] Giri S,Hyde D,Hollinger M.Effect of antibody to transforming growth factor ? on bleomycin induced accumulation of lung collagen in mice. Thorax.1993;48:959–66.
[60] Broekelman T,Limper A,Colby T, et al. Transforming growth factor beta-1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis.Proc Natl Acad Sci USA.1991;88:6642–6.
[61] Zhang H,Phan S.Inhibition of myofibroblast apoptosis by transforming growth factor ?1. Am J Respir Cell Mol Bio.1999;21:658–65.)
[62] Kenyon NJ, Ward RW, Grew GM,et al.TGF-?1 causes airway fibrosis and increased collagen I and III mRNA in mice. Thorax.2003;58:772-777.)
[63] Lee, SS, Won, TB,Kim, JW,et al. Effects of Dexamethasone on the Expression of Transforming Growth Factor-[beta] in the Mouse Model of Allergic Rhinitis. Laryngoscope. 2007;117(8):1323-1328.
[64] 于睿莉,朱冬冬,董震.中华耳鼻咽喉头颈外科杂志.2006;41(10):773-776.
[65] Kranenburg AR. Willems-Widyastuti A. Mooi WJ,et al.Chronic obstructive pulmonary disease is associated with enhanced bronchial expression of FGF-1,FGF-2,and FGFR-1.Journal of Pathology.2005;206(1):28-38.
[66] Shute JK,Solic N,Shimizu J,et al.Epithelial expression and release of FGF-2 from heparan sulphate binding sites in bronchial tissue in asthma.Thorax.2004,;59: 557-562.
1. 佘文煜,董震。实验性变应性鼻炎鼻黏膜组织重塑的特点。中华耳鼻咽喉头颈外科杂志,2006,41:48—53。
2. Bousquet J, Jacot W, Vignola AM, Bachert C, Van Cauwenberge P. Allergic rhinitis: a disease remodeling the upper airways? J Allergy Clin Immunol. 2004 Jan;113(1):43-9.
3. Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med 2000;161:1720-45.
4. P A Beckett, P H Howarth. Pharmacotherapy and airway remodeling in asthma?.Thorax 2003;58:163-174.
5. Bousquet J, Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol.2001.108(Supp15):147-334.
6. Komai M, Tanaka H, Masuda T, Nagao K, Ishizaki M, Sawada M, Nagai H. Role of Th2 responses in the development of allergen-induced airway remodeling in a murine model of allergic asthma. Brithish Journal of Pharmacology.2003,138(5):919-920.
7. Robert J, Ho mer and Jack A, Elias. Airway remodeling in asthma: Therapeutic implications ofmechanisms. Physiology,2005.20:28-35.
8. Vignola AM, Chanez P, Chiappara G, et al. Transforming growth factor-? expression in mucosal biopsies in asthma and chronic bronchitis. Am J Respir Crit Care Med 1997;160:1001–8.
9. Redington A, Madden J, Frew A, et al. Transforming growth factor ?1 in asthma: measurement in bronchoalveolar lavage fluid. Am J Respir Crit Care Med 1997;156:642–7.
10. N J Kenyon, R W Ward, G McGrew and J A Last. TGF-?1 causes airway fibrosis and increased collagen I and III mRNA in mice. Thorax 2003;58:772-777.
11. Hu Peng,Abha Sahni,Philip Fay,et al. Identification of a binding site on human FGF-2 for fibrinogen. Blood,2004;103(6), pp. 2114-2120
12. Ynuk Bosse, Charles Thompson, Jana Stankova, and Marek Rola-Pleszczynski. FGF-2 and TGF-β1 Synergism in Human bronchial smooth muscle cell proliferation.Am.J.Respir.Cell Mol.Biol. Jan 2006;10,1165/rcmb.2005-0309oc.
13. Ward C, Walters H. Airway wall remodeling: the influence of corticosteroids. Current Opinion in Allergy & Clinical Immunology.2005;5(1):43-48.
14. Ann Hoeben, Bart Landuyt, Martin S, Highley, Hans Wildiers, Allan T. Van Osterom and Ernst A. De Bruijn. Vascular Endothelial growth factor and angiogenesis. Pharmacol Rev 2004; 56: 549-580.
15. Weiner JM, Abramson JM, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomized controlled trials. BMJ 1998;317:1624-1629.
16. Peter J, Barnes D M, D Sc. Inhaled glucocorticoids for Asthma. The New England Journal of Medicine. 1995;332:868-875.
17. Pascal Chanez, Arnaud Bourdin, Isabelle Vachier, Philippe Godard, Jean Bousquet and A. M. Vignola. Effects of Inhaled Corticosteroids on Pathology in Asthma and Chronic Obstructive Pulmonary Disease. The Proceedings of the American Thoracic Society .2004;1:184-190.
18. Boulet LP, Turcotte H, Laviolette M, Naud F, Bernier MC, Martel S, Chakir J. Airway hyperresponsiveness, inflammation, and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma: influence of inhaled corticosteroids. Am J Respir Crit Care Med 2000;162:1308–1313.
19. Ward C, Pais M, Bish R, Reid D, Feltis B, Johns D, Walters EH. Airway inflammation, basement membrane thickening and bronchial hyperresponsiveness in asthma. Thorax 2002;57:309–316.
20. Grol MH, Gerritsen J, Vonk JM, et al. Risk factors for growth and decline of lung function in asthmatic individuals up to age 42 years. A 30-year follow-up study. Am J Respir Crit Care Med 1999;160:1830–7.
21. Marina Miller, Jae Youn Cho, Kirsti McElwain, Shauna McElwain, Jung Yeon Shim, Michael Manni, Ji Sun Baek, and David H Broide. Corticosteroids prevent myofibroblast accumulation and airway remodeling in mice. Am J Physiol Lung Cell Mol Physiol, Jan 2006; 290: L162-L169.
22. Laitinen A, Altraja A, Kampe M, Linden M, Virtanen I, Laitinen LA. Tenascin is increased in airway basement membrane of asthmatics and decreased by an inhaled steroid. Am J Respir CritCare Med 1997;156:951–958.
23. Darren Fernandes, Elizabeth Guida, Valentina Koutsoubos, Trudi Harris, Peter Vadiveloo, John W. Wilson, and Alastair G. Stewart. Glucocorticoids Inhibit Proliferation, Cyclin D1 Expression, and Retinoblastoma Protein Phosphorylation, but Not Activity of the Extracellular-Regulated Kinases in Human Cultured Airway Smooth Muscle. Am.J.Respir.Cell Mol.Biol. 1999; 21(1): 77-88.
24. Wenju Lu, Erik P. Lillehoj, and K. Chul Kim. Effects of dexamethasone on Muc5ac mucin production by primary airway goblet cells. Am J Physiol Lung Cell Mol Physiol 2005;288: L52-L60.
25. G Horvath and A Wanner. Inhaled corticosteroids: effects on the airway vasculature in bronchial asthma. Eur Respir J 2006; 27:172-187.
26. Bernadette E Orsida, Xun Li, Bernadette Hickey, Frank Thien, John W Wilson, E Haydn Walters. Vascularity in asthmatic airways: relation to inhaled steroid dose. Thorax 1999;54:289-295
27. Wignarajah D, Zheng L,Harding R,et al. Inhaled corticosteroids and VEGF concentrations in asthmatic bronchoalveolar lavage fluid.Thorax 2003;58(Suppl3):15.
28. McCormack, Paul L, Plosker, Greg L. Inhaled mometasone furoate: a review of its use in persistent asthma in adults and adolescents. Adis Drug Evaluation. 2006;volume66(8):pp 1151-1168.
29. 顾瑞金.糖皮质激素为中重度变应性鼻炎治疗的一线用药.中华耳鼻咽喉科杂志.2004;9:574-576.
30. Richards DH & Scadding GK. Inhaled and intranasal steroids: the differences explained in terms of potential for growth effects. Allergy 2000; 55:S252.
31. A. F. Holm and W. J. Fokkens. Topical corticosteroids in allergic rhinitis; effects on nasal inflammatory cells and nasal mucosa. Clinical & Experimental Allergy. 2001;529.