支气管哮喘气道重塑平滑肌增生机制

支气管哮喘是严重影响人类正常生活的慢性疾病之一,尤其是在气道重塑发生之后。由于气道重塑的不可逆,使支气管哮喘的治疗陷入瓶颈状态。气道重塑最主要的病理学改变为气道平滑肌细胞增殖导致的平滑肌层增厚,其原因是机体慢性炎症和长期免疫应答,那么参与炎症反应和免疫应答的细胞因子以及平滑肌细胞的来源就成为研究气道重塑的重要途径。在此,对近几年的研究作一综述。     

气道平滑肌细胞作为免疫调节细胞与支气管哮喘炎症的关系

气道平滑肌不仅能调节支气管收缩,而且与支气管哮喘气道炎症和气道重塑的发生、发展密切相关.近年研究表明,气道平滑肌细胞在支气管哮喘的免疫调节、气道炎症反应方面起着重要免疫调控作用.     

气道平滑肌细胞作为免疫调节细胞与支气管哮喘炎症的关系

气道平滑肌不仅能调节支气管收缩,而且与支气管哮喘气道炎症和气道重塑的发生、发展密切相关。近年研究表明,气道平滑肌细胞在支气管哮喘的免疫调节、气道炎症反应方面起着重要免疫调控作用。     

转化生长因子β在支气管哮喘气道平滑肌重塑中的作用

支气管哮喘(简称哮喘)是一种气道慢性炎症,持续的气道炎症导致气道重塑、不完全可逆的气流受限和进行性的肺功能受损.平滑肌细胞的增殖(包括增生和肥大)是哮喘气道重塑的特征性改变,是哮喘气道反应性和严重程度相关的重要因素之一.转化生长因子β(TGF-β)能够诱导分化、炎症、增生以及凋亡等多种细胞反应,促进平滑肌细胞的增生、肥大和迁移,在气道重塑中发挥重要作用.减少TGF-β的产生以及控制TGF-β的效应有利于对慢性哮喘气道重塑的干预治疗.     

神经信号转导通路与气道重塑

支气管哮喘是一种由多种细胞和细胞组分参与的气道慢性炎症性疾病,临床上以气道高反应性与气道重塑为主要特征,而气道重塑是其慢性病程中重要的病理学改变,主要表现为炎症细胞浸润和腺体增生肥大,细胞外基质沉积、基底膜以及气道平滑肌增厚。近年来,气道重塑在哮喘发病中的作用     

转化生长因子β在支气管哮喘气道平滑肌重塑中的作用

支气管哮喘（简称哮喘）是一种气道慢性炎症,持续的气道炎症导致气道重塑、不完全可逆的气流受限和进行性的肺功能受损。平滑肌细胞的增殖（包括增生和肥大）是哮喘气道重塑的特征性改变,是哮喘气道反应性和严重程度相关的重要因素之一。转化生长因子β（TGF-β）能够诱导分化、炎症、增生以及凋亡等多种细胞反应,促进平滑肌细胞的增生、肥大和迁移,在气道重塑中发挥重要作用。减少TGF-β的产生以及控制TGF-β的效应有利于对慢性哮喘气道重塑的干预治疗。     

合成/增殖表型气道平滑肌在支气管哮喘发病中的作用

气道慢性炎症与气道重建是支气管哮喘的重要特征,与气道平滑肌的功能状况密切相关.近年研究发现,气道平滑肌细胞可合成和表达多种调节因子,在支气管哮喘的发病机制中起着重要的免疫调节功能.     

Rho/ROCK信号转导通路与支气管哮喘气道重塑

支气管哮喘(简称哮喘)是多种细胞及其组分参与的慢性非特异性炎症性疾病,气道反复炎症损伤与修复造成的气道重塑是哮喘主要的病理生理学特征,预防气道重塑是哮喘干预治疗的重要潜在靶点,是改善哮喘预后的重要手段.Rho通过激活下游效应物Rho相关卷曲螺旋形成蛋白激酶(Rho associated coiled coil fotruing protein kinase,ROCK)作用于气道平滑肌细胞及调节细胞因子和炎性因子等的产生,在哮喘气道重塑的形成与发展中起关键的作用,ROCK抑制剂能有效抑制哮喘动物模型的气道炎症和气道重塑作用.     

支气管哮喘气道重塑研究进展

支气管哮喘(简称哮喘)是以气道慢性炎症和气道重塑为基本特征的慢性疾病.气道重塑的确切机制尚不清楚,目前认为主要与气道慢性炎症有关,上皮损伤及上皮间充质营养单位再活化在气道重塑发病中也起重要作用.治疗哮喘的传统药物对气道重塑作用有限,近年应用抗肿瘤坏死因子α、CpG-ODN、抗IgE抗体和抗Th2细胞因子等免疫调节剂治疗气道重塑,支气管热整形术是有创性治疗技术.     

哮喘气道重塑及其药物干预治疗

支气管哮喘是气道的慢性炎症性疾病。近年来研究发现．除气道炎症外，哮喘的另一重要特征是气道壁的结构改变——气道重塑。目前认为气道重塑是导致气道不可逆性阻塞和气道高反应性的主要病理基础。气道重塑的组织学特征包括气道壁增厚．上皮下纤维化，平滑肌细胞增生、肥大．杯状细胞和黏液腺增生、肥大。血管生成。现多认为气道重塑是在炎症基础上     

急性期和慢性期哮喘小鼠模型在哮喘致病过程中的对比研究

目的 比较卵清蛋白(ovalbumin,OVA)诱导的急性期和慢性期哮喘小鼠模型在气道炎症、气道重塑和气道高反应方面的差异,明确在哮喘致病过程中肺组织的病理变化.方法 48只BALB/c小鼠随机分为急性组和慢性组,其中急性组包括正常对照组(A1组)和急性哮喘组(A2组),慢性组包括正常对照组(B1组)和慢性哮喘组(B2组).OVA致敏和激发方法分别构建急性早期哮喘模型和慢性期哮喘模型后,测定气道阻力,BALF细胞计数和分类计数,酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)检测IL-4、IL-5、转化生长因子-β1(transforming growth factor-β1,TGF-β1)、血管内皮生长因子(vascular endothelial growth factor,VEGF)和γ-干扰素(interferon-γ,IFN-γ).HE染色观察气道炎症,AB-PAS和Masson染色测定气道重塑.结果 与正常小鼠相比,A2组和B2组小鼠气道阻力均明显升高,但B2组小鼠气道阻力在基础值即发生明显改变.相比于慢性组哮喘小鼠,急性组哮喘小鼠BALF中细胞总数和嗜酸粒细胞数,IL-4、IL-5和IFN-γ水平,肺组织气道血管周围炎症细胞聚集,以及气道黏液分泌水平等炎症性改变更为明显.相比于A2组,B2组哮喘小鼠BALF中TGF-β1和VEGF水平,气道平滑肌增厚,上皮下胶原沉积,上皮下纤维化等改变更为显著.结论 在急性早期哮喘中主要是以炎症性改变为主,但在哮喘早期即开始出现轻度的重塑性改变;而在慢性期哮喘中虽然存在炎症性改变,但影响哮喘症状的因素却主要以器质性改变为主.     

Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a comparison.

Chronic inflammation in asthma and chronic obstructive pulmonary disease drives pathological structural remodelling of the airways. Using tiotropium bromide, acetylcholine was recently identified as playing a major regulatory role in airway smooth muscle remodelling in a guinea pig model of ongoing allergic asthma. The aim of the present study was to investigate other aspects of airway remodelling and to compare the effectiveness of tiotropium to the glucocorticosteroid budesonide. Ovalbumin-sensitised guinea pigs were challenged for 12 weeks with aerosolised ovalbumin. The ovalbumin induced airway smooth muscle thickening, hypercontractility of tracheal smooth muscle, increased pulmonary contractile protein (smooth-muscle myosin) abundance, mucous gland hypertrophy, an increase in mucin 5 subtypes A and C (MUC5AC)-positive goblet cell numbers and eosinophilia. It was reported previously that treatment with tiotropium inhibits airway smooth muscle thickening and contractile protein expression, and prevents tracheal hypercontractility. This study demonstrates that tiotropium also fully prevented allergen-induced mucous gland hypertrophy, and partially reduced the increase in MUC5AC-positive goblet cell numbers and eosinophil infiltration. Treatment with budesonide also prevented airway smooth muscle thickening, contractile protein expression, tracheal hypercontractility and mucous gland hypertrophy, and partially reduced MUC5AC-positive goblet cell numbers and eosinophilia. This study demonstrates that tiotropium and budesonide are similarly effective in inhibiting several aspects of airway remodelling, providing further evidence that the beneficial effects of tiotropium bromide might exceed those of bronchodilation.     

Animal models of airway inflammation and airway smooth muscle remodelling in asthma

Asthma is a complex disease that involves chronic inflammation and subsequent decline in airway function. The widespread use of animal models has greatly contributed to our understanding of the cellular and molecular pathways underlying human allergic asthma. Animal models of allergic asthma include smaller animal models which offer ‘ease of use’ and availability of reagents, and larger animal models that may be used to address aspects of allergic airways disease not possible in humans or smaller animal models. This review examines the application and suitability of various animal models for studying mechanisms of airway inflammation and tissue remodelling in allergic asthma, with a specific focus on airway smooth muscle.     

维生素D调节支气管哮喘气道平滑肌的研究进展

气道平滑肌的过度增生、肥大及功能异常,可能是支气管哮喘（简称哮喘）的发病机制之一。新近研究发现,除了对骨骼和钙代谢有明确的作用,维生素D还可调节气道平滑肌的增殖、收缩,并在哮喘的免疫调节方面起着重要的调控作用,从而影响气道炎症、气道重塑等哮喘的病理生理过程。本文就维生素D调节哮喘气道平滑肌的研究进展作一综述。     

Clinical relevance of airway remodelling in airway diseases.

Asthma and chronic obstructive pulmonary disease (COPD) are characterised by airflow obstruction, airway remodelling (measurable structural change) and inflammation. The present review will examine the relationship between airway remodelling in these two conditions with respect to symptoms, abnormal lung function, airway hyperresponsiveness and decline in lung function. The potential for remodelling to be a protective response will also be discussed. Asthma is associated with variable symptoms and changes in lung function and also fixed abnormalities of lung function and an increased rate of decline in lung function with age. There is a relative preservation of the relaxed airway lumen dimensions, prominent thickening of the smooth muscle layer and reduced airway distensibility. The severity of asthma is related to the degree of airway remodelling, which is most marked in cases of fatal asthma. In COPD, symptoms are persistent and predictable but also progressive and are related to fixed abnormalities of lung function. Remodelling is associated with narrowing of the airway lumen and an increased thickness of the airway wall, although not usually to the extent seen in asthma. COPD is most often due to smoking where there is also remodelling of the parenchyma that may contribute to symptoms.     

Airway remodelling in asthma: From benchside to clinical practice

Airway remodelling refers to the structural changes that occur in both large and small airways relevant to miscellaneous diseases including asthma. In asthma, airway structural changes include subepithelial fibrosis, increased smooth muscle mass, gland enlargement, neovascularization and epithelial alterations. Although controversial, airway remodelling is commonly attributed to an underlying chronic inflammatory process. These remodelling changes contribute to thickening of airway walls and, consequently, lead to airway narrowing, bronchial hyper-responsiveness, airway edema and mucous hypersecretion. Airway remodelling is associated with poor clinical outcomes among asthmatic patients. Early diagnosis and prevention of airway remodelling has the potential to decrease disease severity, improve control and prevent disease expression. The relationship between structural changes and clinical and functional abnormalities clearly deserves further investigation. The present review briefly describes the characteristic features of airway remodelling observed in asthma, its clinical consequences and relevance for physicians, and its modulation by therapeutic approaches used in the treatment of asthmatic patients.     

The role of airway smooth muscle in the pathogenesis of airway wall remodeling in chronic obstructive pulmonary disease

Airway wall remodeling processes are present in the small airways of patients with chronic obstructive pulmonary disease, consisting of tissue repair and epithelial metaplasia that contribute to airway wall thickening and airflow obstruction. With increasing disease severity, there is also increased mucous metaplasia and submucosal gland hypertrophy, peribronchial fibrosis, and an increase in airway smooth muscle mass. Apart from its contractile properties, airway smooth muscle produces inflammatory cytokines, proteases, and growth factors, which may contribute to the remodeling process and induce phenotypic changes of the muscle. Airflow limitation responds minimally to beta-agonists and corticosteroid therapy, unlike asthma, perhaps because of alterations in beta-receptor or glucocorticoid receptor numbers, alterations in receptor signaling, or the constrictive limitation imposed by peribronchial fibrosis. Better response is observed with the combination of inhaled long-acting beta-agonists and corticosteroids. This could result from effects at the level of airway smooth muscle. Airway wall remodeling may involve the release of growth factors from inflammatory or resident cells. The influence of smoking cessation or of current therapies on airway wall remodeling is unknown. Specific therapies for airway wall remodeling may be necessary, together with noninvasive methods of imaging small airway wall remodeling to assess responses.