吸入维生素A和皮质激素对大鼠哮喘性肺炎的疗效及TSLP表达的影响

目的:观察胸腺与肺的胸腺基质淋巴细胞生成素(TSLP)和Th因子在病程发展中变化,分析吸入维生素A(VA)与皮质激素对哮喘性肺炎疗效。方法:卵蛋白激发大鼠哮喘4周后休息1周,VA与皮质激素吸入治疗1周,吸入90%乙醇液作为哮喘组。通过免疫荧光染色、组织化学染色等法检查胸腺与肺。结果:激发第4～5周后,哮喘组胸腺与肺TSLP阳性细胞、肺泡巨噬细胞(AM)较多,胸腺和脾增生,血Th2因子升高,肺部炎症逐渐加重;VA组第4周胸腺与肺TSLP和Th2因子表达均较低;第5周TSLP轻度增加,胸腺、脾T细胞区增生由强转弱,AM明显增多,肺炎症逐渐消退。激素组第4～5周胸腺和肺TSLP、Th2因子表达低,胸腺、脾增生渐强。AM数量少,肺炎症渐重。结论:激发哮喘期间TSLP表达增强伴有Th2类反应,VA和皮质激素均抑制TSLP与Th2因子表达,但VA促进T淋巴细胞增生与AM清除抗原功能,停药后肺炎症逐渐消退;皮质激素停药后炎症加重。     

口服柔嫩梭菌对OVA致敏小鼠气道炎症的影响

目的 在动物水平探索口服柔嫩梭菌(Clostridium leptum)对哮喘小鼠气道炎症的影响.方法 建立OVA致敏的BALB/c小鼠哮喘模型,依据检测气道炎症情况和气道反应性确定哮喘模型构建成功.30只BALB/c小鼠随机分为3组:正常对照组,安慰剂组和口服柔嫩梭菌治疗组,每组10只.通过HE染色检测小鼠肺组织病理变化,细胞计数检测肺泡灌洗液中炎性细胞(嗜酸性粒细胞、中性粒细胞、淋巴细胞、巨噬细胞)的数目,ELISA方法检测肺泡灌洗液中炎性因子(IL4、IL-5、IL-13)的表达情况,并检测各组小鼠的气道反应性.结果 验证OVA致敏哮喘小鼠模型构建成功;口服柔嫩梭菌可显著减轻OVA致敏小鼠的气道高反应性,气道炎症细胞浸润和炎性细胞因子分泌(P＜0.05).结论 口服柔嫩梭菌可显著减轻OVA致敏小鼠的气道炎症和气道高反应性,这可能为哮喘治疗提供新思路.     

小鼠哮喘发作过程中相关炎症因子的动态变化

目的:研究实验性哮喘小鼠模型在诱导哮喘发作不同时间点外周血中细胞因子IL-13、Eotaxin、MCP-1和TNF-α以及肺部浸润的炎症细胞数量变化。方法:将25只健康6-8周龄的雌性BALB/c小鼠随机分成模型组和对照组。利用卵清蛋白(OVA)诱导建立小鼠哮喘模型,模型组(Asthma)小鼠于第0、7天经腹腔注射卵清蛋白(OVA)致敏小鼠。第14-20天连续7天用1%OVA雾化激发小鼠哮喘发作,每次20 min,观察临床症状。正常对照组(Control)小鼠以0.9%NaCL代替0VA进行腹腔注射和雾化吸入。比较两组小鼠肺组织病理切片HE染色结果、肺泡灌洗液(BALF)中炎性细胞分类计数及细胞因子IL-13、Eotaxin、MCP-1和TNF-α的浓度变化。结果:模型组小鼠BALF中IL-13的水平在试验早期(致敏2天)即开始上升达68.9±4.34,此时Eotaxin和MCP-1未见明显升高;致敏7天时IL-13、Eotaxin和MCP-1均明显高于对照组,分别为88.3±3.39、67.4±4.24和38.9±3.1;激发1天组小鼠BALF中IL-13、Eotaxin和MCP-1浓度持续增高至最后一次激发后1天;而TNF-α在激发1天时出现明显升高达136.9±11.9,持续到最后一次激发后1天;从激发1天肺泡灌洗液染色显微镜下观察明以淋巴细胞和嗜酸性粒细胞浸润为主。肺组织HE染色显示哮喘组小鼠气道上皮有不同程度脱落,支气管平滑肌显著增厚,血管周围水肿,炎性细胞浸润。结论:在哮喘发生过程中,IL-13水平在致敏初期即开始升高,随着继续给予OVA,Eotaxin和MCP-1水平呈现显著增高;并伴随越来越多炎症细胞在肺部浸润,TNF-α水平出现缓慢增高,进而加重哮喘发作。     

结核感染小鼠肺部病理变化与T细胞免疫关系的实验研究

目的探讨结核病小鼠肺部病理变化与T细胞亚群的关系。方法将60只C57BL小鼠随机分为3组,每组20只。结核病模型组小鼠经球后静脉丛注射人型结核分枝杆菌标准毒力珠（H37RV）;免疫调节剂组结核病模型小鼠于H37RV感染后第3、10、17天分别肌注22.5μg母牛分枝杆菌菌苗（微卡菌苗）;正常对照组小鼠未做处理。感染4周后,留取外周血用流式细胞仪测定T细胞亚群;取肺组织,采用常规苏木精-伊红染色和抗酸染色后病理切片观察病理变化。结果结核病模型组小鼠大部分肺组织实变,多数肺泡腔消失,肺泡隔重度增宽,肺间质内可见大量炎性细胞浸润,浸润细胞以中性粒细胞为主,淋巴细胞较少。残存的肺泡腔中有红细胞、纤维素渗出。肺实变区内分布大量的紫红色结核分枝杆菌,主要存在于单核-巨噬细胞胞质内。外周血T细胞亚群的相对比率明显减少。免疫调节剂组肺组织病变和结核病模型组大致相似,但实变病灶较少,多数肺泡腔存在,肺泡隔内浸润淋巴细胞较多,肺泡腔内有渗出单核-巨噬细胞。肺实变区内结核分枝杆菌明显少于结核病模型组,CD3^＋与CD4^＋T细胞比例增加,能显著增加γδT细胞比例。结论微卡菌苗可增强结核病小鼠的免疫功能,使肺实变病灶较少和病灶内结核分枝杆菌明显减少,肺泡腔内单核-巨噬细胞增多,为免疫调节剂辅助治疗结核病提供理论依据。     

甲状腺激素对胸腺上皮细胞CK19蛋白表达的影响

目的探讨甲状腺激素对胸腺的发育的影响及可能的机制。方法将12只怀孕4d的大鼠随机分成A组和B组,A组正常饮水,B组孕鼠供以含有0．02％甲巯咪唑的饮水制备仔鼠甲状腺功能低下动物模型,将A组的仔鼠随机分成对照组和甲状腺素钠组,将B组的仔鼠随机分成甲低组和甲低＋甲状腺素钠组。甲状腺素钠组和甲低＋甲状腺素钠组于出生后15d给予腹腔注射甲状腺素钠（0．5mg／kg体重,1次／d）,连续给药25d。所有动物于出生后40d麻醉处死,测定仔鼠的胸腺重量及脏器指数;采用放射免疫技术测定仔鼠血清中三碘甲状腺原氨酸（triiodothyronine,T3）、四碘甲状腺原氨酸（tetraiodothyronine,T4）、促甲状腺激素（thyroid—stimulating hormone,TSH）水平,免疫组织化学技术检测胸腺上皮细胞细胞角蛋白19（cytokeratin 19,CK19）蛋白的表达量。结果与对照组比较,甲状腺素钠组仔鼠血清中T3、T4显著升高,TSH减少,胸腺重量增大;甲低组仔鼠血清中T3、T4明显降低,TSH显著增高,胸腺重量降低,胸腺上皮细胞CK19蛋白表达减少。与甲低组比较,甲低＋甲状腺素钠组仔鼠血清中T3、T4升高,TSH降低,胸腺指数增大,胸腺上皮细胞CK19蛋白的表达明显增多。结论甲状腺激素可以通过影响胸腺上皮细胞CK19的表达量,使胸腺发育或退化。     

中华鳖造血和免疫器官的个体发育

采用常规孵化的中华鳖胚胎为材料,对不同发育时期造血和免疫器官进行了组织学研究,描述了卵黄囊、胸腺、肝、脾、肾以及骨髓的形态结构变化。发现胚胎期首先出现的造血器官是卵黄囊。此后,卵黄囊的造血干细胞出现在胚体的血循环中,造血功能相继在胚胎胸腺、肝、脾、骨髓(可能还包括肾)中产生。胸腺是中华鳖免疫系统发育的第一个淋巴器官,来自卵黄囊的干细胞在此先分化成小淋巴细胞,然后再迁移至脾脏。脾脏发育中首先出现各发育阶段的红细胞、嗜酸性的细胞和少量粒细胞,淋巴细胞出现较晚,未发现淋巴小结。在胚胎期肝脏发育过程中可见不同发育时期的红细胞和嗜酸性的细胞。在肾的发育过程中,尚可观察到嗜酸性的细胞和类似头肾组织的细胞团。直至出壳前,骨髓内方可见各发育阶段的各系细胞[动物学报49(2)：238—247,2003]。     

光,电镜观察小鼠呼吸道合胞病毒性肺炎的免疫病理改变

Ｂａｌｂ／ｃ小鼠经鼻吸入呼吸道合胞病毒（ＲＳＶ）悬液感染成ＲＳＶ肺炎。于感染第５天后连续隔日取肺,光镜与透射电镜检查。感染第５～７天,肺组织病理改变最严重,多数小鼠表现为间质淋巴细胞（ＬＣ）套状浸润,肺泡隔增宽;少数小鼠出现间质内大量ＬＣ浸润与肺泡内大量单个核细胞渗出的两种病理改变。病毒包涵体出现于肺泡上皮细胞内,细胞受感染后发生肿胀、坏死。Ⅰ型细胞核周胞质内有核衣壳复制,表面病毒芽生形成长短不等的丝状体。第９天,肺泡隔增宽与间质ＬＣ浸润逐渐减轻。第１２天,病毒包涵体明显减少。     

中华鳖胸腺显微和亚显微结构及其在进化上的意义

应用透射电子显微镜观察了中华鳖胸腺的显微和亚显微结构。发现中华鳖胸腺从结构上可分为皮质和髓质,皮质富含淋巴细胞,髓质富含上皮性网状细胞。在各发育期中华鳖胸腺皮质、髓质交界处和髓质区有明显的囊状胸腺小体和交错突细胞。在２００ｇ以上的成年鳖胸腺内发现有同心圆状胸腺小体。电镜下,胸腺内淋巴细胞分为大、中、小３型。上皮性网状细胞从亚显微结构上分为支持型和分泌型。胸腺囊包括细胞内囊和细胞间囊,以细胞内囊居多     

胸腺对法氏囊滤泡及脾脏B淋巴细胞区发育的影响

Siskind 等(1979)发现胸腺或胸腺细胞对B细胞接触抗原前的发育有影响;未成熟B细胞对胸腺依赖性抗原反应而产生异质性抗体的能力受胸腺的控制。Bhogal 等(1984)进一步指出,鸡法氏囊 B细胞的发育存在一个胸腺依赖的阶段,胸腺对法氏囊的发育可能存在体液性影响。本文通过手术去除胸腺、注射胸腺提取液等实验,观察法氏囊和脾脏淋巴细胞的显微和亚显微结构的变化,探讨胸腺对法氏囊滤泡及脾脏 B细胞区发育的影响。 材料和方法:实验用初生雏鸡是从山东省农科院购买的莱杭雏鸡,常规饲养。实验每组 10只雏鸡,分以下几组进行:1.手术切除胸腺组,取刚孵出的雏鸡,手术去除胸腺;2.手术切除胸腺并注射同龄鸡     

婴儿型双歧杆菌对哮喘小鼠气道炎症的作用研究

目的探讨婴儿型双歧杆菌对气道过敏小鼠的气道炎症作用及其机制。方法 6周龄BALB/c雄性小鼠40只,随机分为4组:阴性对照组、哮喘组、婴儿型双歧杆菌预防组和婴儿型双歧杆菌治疗组。哮喘组、预防组和治疗组用卵清蛋白(Ovalbvmin,OVA)进行致敏和激发诱发哮喘,阴性对照组用生理盐水进行致敏和激发。预防组第0至14天灌胃菌液;治疗组第15至28天灌胃菌液;阴性对照组和哮喘组全程灌胃生理盐水作对照。观察小鼠气道过敏表现;计数肺泡灌洗液(Bronchoalveolar lavage fluid,BALF)中细胞总数评估气道炎症程度;肺组织行HE染色;ELISA法测定血清中IL-10、OVA特异性IgE和OVA特异性IgG1的浓度以及肺泡灌洗液中细胞因子IL-4、IL-5、IL-10、IL-13和IFN-γ的浓度。结果 (1)哮喘组小鼠在激发后出现搔抓口鼻、竖毛、打喷嚏、腹肌扇动、弓背直立、二便失禁以及体重下降等表现,预防组和治疗组的症状较轻。(2)预防组和治疗组BALF细胞数量明显低于哮喘组(P0.05)。(3)肺组织HE染色后,哮喘组小鼠肺组织出现明显的炎症细胞浸润,预防组和治疗组肺组织炎症明显减轻。(4)预防组和治疗组血清OVA特异性IgE浓度明显低于哮喘组(P0.05),并且预防组低于治疗组(P0.05);治疗组血清OVA特异性IgG1浓度明显低于哮喘组和预防组(P0.05);预防组和治疗组血清IL-10浓度明显高于哮喘组(P0.05),且治疗组高于预防组(P0.05);(5)预防组和治疗组肺泡灌洗液中IL-4、IL-13含量明显低于哮喘组(P0.05);IL-5、IL-10、IFN-γ各组浓度都较低,未测出有效浓度。结论口服婴儿型双歧杆菌可以减轻过敏症状,降低肺组织炎症浸润程度,抑制Th2免疫反应。     

Developmental studies on expression of monoclonal antibody-defined cytokeratins by thymic epithelial cells from normal and autoimmune mice

A major component of the thymic microenvironment is a network of thymic epithelial cells (TEC) which are able to express class II major histocompatibility complex products and to secrete thymic hormones. In the present investigation, we used a panel of anti-cytokeratin (CK) antibodies to establish distinct cytokeratin-defined TEC subsets. Four subpopulations were identified. One, in the cortex, is defined by anti-CK8 and anti-CK18 monoclonal antibodies (MAb). The other three subsets are medullary, two minor ones respectively reactive with anti-CK19 and KL1 monoclonal antibodies (the latter being specific for CK3 and 10), and a major one characterized by negative reaction with the above-mentioned MAb but strongly positive after labeling with a polyclonal (and polyspecific) anti-keratin immunoserum. Ontogenetic studies revealed that the CK8+/18+ TEC subset is the first to be detected in fetal life. Moreover, the numbers of CK3/10+ cells and CK19+ cells decrease in aging normal mice, a phenomenon that seems to occur early in autoimmune mice. We also observed that these two medullary TEC subsets are sensitive to high-dose in vivo treatment with hydrocortisone, which stimulates a dramatic increase in CK3/10+ cells and a certain decrease in CK19+ cells. Our results indicate that a number of mouse TEC subsets can be distinguished by cytokeratin expression. Such a strategy can be applied to analyze TEC sensitivity to drugs and might also be useful to further understanding of differential TEC function regarding intrathymic T-cell differentiation.     

Immunohistochemical studies on a human thymic epithelial cell subset defined by the anti-cytokeratin 18 monoclonal antibody

Summary Two monoclonal antibodies respectively recognizing cytokeratins (CK) 18 and 19 were applied to the human thymic epithelium (in vivo and in vitro) in normal and pathological conditions, including 12 thymomas. We observed that in both normal and hyperplastic thymuses (from patients with myasthenia gravis) virtually the entire epithelial network was CK19-positive as were the majority of cells growing in culture. In four thymomas, however, the expression of cytokeratin 19 was not detected by immunofluorescence. On the other hand, CK18 was expressed by a discrete subset of medullary thymic epithelial cells in normal and in hyperplastic thymuses. Among the thymomas a large majority was either negative or contained few isolated CK18-positive cells scattered within the tumour. Conversely, in the two undifferentiated epithelial thymomas, virtually all the tumoral network was strongly labeled with the anti-CK18 monoclonal antibody. The present investigation thus not only defines the human thymic epithelial cell subset on the basis of differential cytokeratin expression but also indicates that anti-CK antibodies with single cytokeratin specificities can be regarded as useful tools to study the heterogeneity of thymomas.     

Age-related changes in rat thymic epithelial cells

We investigated age-related changes in immunocytochemical localisation of cytokeratin 16 (CK16) in thymuses of female Wistar rats at various stages of adult life (months 1, 3, 6, 12). Within the 1 st month of life, distribution of CK typical for individual subsets of thymic epithelial cells (TEC) was observed. The most numerous CK16+ TEC were observed in the outer region of medulla, in the outer cells of Hassall's corpuscles and in the superficial epithelial layer neighbouring the connective tissue of the capsule, septa and vessels of the thymus. In the 3rd month of life, increased intensity of CK16 reaction in superficial TEC was accompanied by increased numbers of CK 16+ TEC in the outer region of the medulla. Age-related alterations in the distribution of the studied markers were evident beginning from the 6th month of life and involved increased expression of CK16 in the superficial layer of TEC, which at the interface with the septa formed stratified epithelium. In parallel, decreased numbers of CK16+ TEC were observed in the outer region of the medulla. Changes in CK16+ TEC distribution of a similar type developed in 12-month old rats and they probably reflected altered functions of some TEC populations and decreased or increased biological activity of other TEC populations.     

A novel cofactor produced by a thymic epithelial cell line: promotion of proliferation of immature thymic lymphocytes by the presence of interleukin-1 and various mitogens

Three thymic epithelial cell lines (TEC1C5, TEC1-4, and TEC2-3) were established from the thymus of newborn C57BL/6 mice. TEC1C5 was revealed to be an interleukin (IL)-1 producing cell line. TEC1-4 produced a cofactor to promote proliferation of double negative (CD4-8-) thymic lymphocytes by the presence of IL-1. Production of the same cofactor was also seen in TEC2-3, but only when it was cultured by the presence of indomethacin. The chemical analysis of the TEC1-4 culture supernatant by ion-exchange column and sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the factor was approximately 35 kDa in molecular weight. The present study revealed that a factor produced by TEC1-4 acted as a cofactor to promote the proliferation of immature T cells stimulated by IL-1 and various mitogens and was considered to be a new one in terms of molecular weight.     

Attenuation of allergen-induced responses in CCR6-/- mice is dependent upon altered pulmonary T lymphocyte activation

We have established a defect in CCR6-/- mice in response to a cockroach allergen airway challenge characterized by decreased IL-5 production, reduced CD4+ T and B cells as well as decreased eosinophil accumulation. To determine the nature of the defect in CCR6-/- mice T lymphocyte populations from allergen-sensitized wild-type mice were transferred into sensitized CCR6-/- mice. The reconstituted response was characterized by an increase in IL-5 levels, eosinophil accumulation, and serum IgE levels in recipient CCR6-/- mice. Analysis of lymphocytes from draining lymph nodes of CCR6+/+ and CCR6-/- sensitized or challenged mice demonstrated a significant decrease in IL-5 and IL-13 production in CCR6-/- mice. In contrast, the systemic response in allergen-rechallenged spleen cells demonstrated no significant alteration in allergen-induced cytokine production. Transfer of isolated splenic T lymphocytes from sensitized CCR6+/+ mice induced airway hyperresponsiveness in wild-type but not CCR6-/- naive mice, suggesting that T cells alone were not sufficient to induce airway hyperresponsiveness in CCR6-/- mice. Additional analysis demonstrated decreased CD11c+, CD11b+ and CD11c, and B220 subsets of dendritic cells in the lungs of CCR6-/- mice after allergen challenge. Using in vitro cell mixing studies with isolated pulmonary CD4+ T cells and CD11c+ cells from CCR6+/+ or CCR6-/- mice, we demonstrate alterations in both CCR6-/- T cells and CCR6-/- pulmonary APCs to elicit IL-5 responses. Altogether, the defect in CCR6-/- mice appears to be primarily due to an alteration in T cell activation, but also appears to include local pulmonary APC defects.     

The glucocorticoid receptor mediates the thymic epithelial cell-induced apoptosis of CD4+8+ thymic lymphoma cells

"Negative selection" and "death by neglect" are governed by apoptotic processes occurring in the thymus that shape the repertoire of maturing T cells. We have previously developed an in vitro model that recapitulates "death by neglect": Co-cultivation of double positive (DP) thymocytes or thymic lymphoma cells (PD1.6) with thymic epithelial cells (TEC) caused TcR-independent apoptosis of the former. We further demonstrated that this apoptosis could be attenuated by aminoglutethimide, an inhibitor of steroid synthesis, suggesting a role of TEC-derived glucocorticoids (GC) in this death process. We have now substantiated the role of the GC-glucocorticoid receptor (GR) axis by using a GC-resistant subline (PD1.6Dex(-)) obtained from the GC-sensitive PD1.6 cells by repeated exposures to increasing doses of dexamethasone (Dex). The PD1.6Dex(-) cells barely express GR and are much less sensitive to TEC-induced apoptosis. Re-expression of GR in PD1.6Dex(-) cells restored their sensitivity to both Dex and TEC, highlighting the central role of GR in these apoptotic processes. Likewise, repeated exposures of PD1.6 cells to TEC led to the selection of TEC-resistant cells (PD1.6TEC(-)) that are insensitive to corticosterone and less sensitive to Dex, though their GR level was only moderately reduced. This is in line with the low levels of corticosterone secreted by TEC. Altogether, our data show that TEC eliminates DP thymic lymphoma cells in a GR-dependent manner and modulates the GC sensitivity of the surviving cells.     

Retinoic acid reverses the airway hyperresponsiveness but not the parenchymal defect that is associated with vitamin A deficiency

Airway hyperresponsiveness (AHR) is influenced by structural components of the bronchial wall, including the smooth muscle and connective tissue elements and the neuromuscular function. AHR is also influenced by parenchymally derived tethering forces on the bronchial wall, which maintain airway caliber by producing outward radial traction. Our previous work has shown that vitamin A-deficient (VAD) rats exhibit cholinergic hyperresponsiveness and a decrease in the expression and function of the muscarinic-2 receptors (M2R). We hypothesized that if decreases in radial traction from airway or parenchymal structures contributed to the VAD-related increase in AHR, then the radial traction would normalize more slowly than VAD-related alterations in neurotransmitter signaling. Rats remained vitamin A sufficient (VAS) or were rendered VAD and then maintained on the VAD diet in the presence or absence of supplementation with all-trans retinoic acid (RA). VAD was associated with an approximately twofold increase in respiratory resistance and elastance compared with VAS rats. Exposure to RA for 12 days but not 4 days restored resistance and elastance to control (VAS) levels. In VAD rats, AHR was accompanied by decreases in bronchial M2R gene expression and function, which were restored after 12 days of RA supplementation. Subepithelial bronchial elastic fibers were decreased by approximately 50% in VAD rats and were significantly restored by RA. The increase in AHR that is associated with VAD is accompanied by decreases in M2R expression and function that can be restored by RA and a reduction in airway elastic fibers that can be partially restored by RA.     

Ontogeny and regulation of IL-7-expressing thymic epithelial cells

Epithelial cells in the thymus produce IL-7, an essential cytokine that promotes the survival, differentiation, and proliferation of thymocytes. We identified IL-7-expressing thymic epithelial cells (TECs) throughout ontogeny and in the adult mouse thymus by in situ hybridization analysis. IL-7 expression is initiated in the thymic fated domain of the early primordium by embryonic day 11.5 and is expressed in a Foxn1-independent pathway. Marked changes occur in the localization and regulation of IL-7-expressing TECs during development. IL-7-expressing TECs are present throughout the early thymic rudiment. In contrast, a major population of IL-7-expressing TECs is localized to the medulla in the adult thymus. Using mouse strains in which thymocyte development is arrested at various stages, we show that fetal and postnatal thymi differ in the frequency and localization of IL-7-expressing TECs. Whereas IL-7 expression is initiated independently of hemopoietic-derived signals during thymic organogenesis, thymocyte-derived signals play an essential role in regulating IL-7 expression in the adult TEC compartment. Moreover, different thymocyte subsets regulate the expression of IL-7 and keratin 5 in adult cortical epithelium, suggesting that despite phenotypic similarities, the cortical TEC compartments of wild-type and RAG-1(-/-) mice are developmentally and functionally distinct.     

气道高反应动物模型的建立与指标检测

目的 通过重新评价卵蛋白致小鼠哮喘模型,寻找一种简便易行的气道高反应动物模型和相应的检测指标,为研发治疗本类疾病药物和研究气道高反应发病机制提供新的实验手段.方法 小鼠采用卵白蛋白（OVA）致敏;致敏后（15～21）d给予10% OVA雾化吸入激发哮喘,在末次激发24 h内测量小鼠辣椒素引咳的半数有效浓度,处死小鼠取肺组织测定匀浆中NO、IL-13、ET-1的含量.结果 卵蛋白致敏模型小鼠随辣椒素浓度的升高其咳嗽反应阳性率、咳嗽次数明显增加（与对照组相比较P〈0.01）.模型组辣椒素引咳的半数有效浓度为89.39 μmol/L,对照组、地塞米松组分别为204.84、220.02 μmol/L;小鼠肺匀浆NO、ET-1、IL-13含量均明显增加,地塞米松可明显抑制NO的升高（与对照组相比较P〈0.01）.结论小鼠经卵蛋白致敏并连续激发7 d与临床气道高反应性（AHR）的多种特征相似,操作简便易行,稳定性高,故可作为气道高反应性的模型.辣椒素引咳阈值的测定、动物肺组织中NO、IL-13、ET-1含量的变化,可作为评价模型严重程度的指标.