布地奈德/福莫特罗对支气管哮喘患者血管内皮生长因子及其受体1表达及气道重塑的调控作用

Budesonide/formoterol decreases expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 1 within airway remodelling in asthma

目的支气管哮喘(简称哮喘)是一种慢性气道炎症疾病,伴随气道高反应性、可逆性气流阻塞和气道重塑。血管生成和微血管重塑在气道慢性炎症过程中可能起到重要的作用。血管内皮生长因子(vascular endothelial growth factor,VEGF)是一种促血管生成因子,其生理作用包括促进内皮细胞存活、增殖和迁移。本研究通过检测哮喘患者气道VEGF和VEGF受体1(VEGFR1)的表达,探讨VEGF和哮喘患者气道重塑的关系以及布地奈德/福莫特罗对哮喘患者气道重塑的调控作用。方法支气管组织来源于2006年4月至11月四川大学华西医院经纤维支气管镜行组织活检。23例为中度哮喘患者,20例为对照组。哮喘患者给予规律吸入布地奈德/福莫特罗4.5/160μg,2次/d,持续半年。VEGF和VEGFR1通过免疫组织化学进行检测。AB-PAS和MassonTrichrome染色用于评估气道重塑程度。结果两组之间年龄和性别差异无统计学意义。而两组之间用力肺活量占预计值%,第一秒用力呼气容积占预计值%,PC20,V75占预计值%,V50占预计值%和V25占预计值%的差异有统计学意义。哮喘组患者气道黏液腺增生、平滑肌增厚、上皮下纤维化以及新生血管增加。与对照组比较,VEGF和VEGFR1阳染细胞数目增多,表达增加。VEGF和VEGFR1表达增加与哮喘患者的气道重塑、气流阻塞和气道高反应性呈正相关。规律吸入布地奈德/福莫特罗6个月后,哮喘患者VEGF和VEGFR1表达减少,气道重塑减轻。结论伴随哮喘患者气道血管生成增多和气道重塑,VEGF和VEGFR1表达增加。规律吸入布地奈德/福莫特罗可以通过减少VEGF和VEGFR1表达而减轻哮喘患者气道重塑。阻断VEGF和VEGFR1可能是治疗哮喘的新策略。

Objective Bronchial asthma(asthma) is a chronic disease characterized by airway inflammation,airway hyperresponsiveness,reversible airway obstruction and airway remodeling.Angiogenesis and microvascular remodeling may play a vital role in chronic inflammatory processes.Vascular endothelial growth factor(VEGF) is a potent angiogenic factor whose activities include endothelial cell survival,proliferation,and migration.In this study we hypothesized that an increased expression of VEGF may exist and complicate with airway remodeling in asthma patients.Budesonide-Formoterol can decrease the expressions of VEGF and VEGF receptor 1(VEGFR1) with airway remodeling in asthma.To this end,we examined the expression levels of VEGF and its receptor in bronchial tissues of patients with asthma to investigate the relationship between VEGF and airway remodeling and the efficiency of Budesonide-Formoterol on the airway remodeling.Methods Bronchial tissues were obtained from fiberoptic bronchoscopy and bronchial biopsy in West China Hospital from April to November in 2006.Thirteen patients were diagnosed as patients with moderate asthma,and other 10 were the control subjects.The patients with asthma were treated with Budesonide-Formoterol for 6 months.The expressions of VEGF and VEGFR1 in bronchial tissues were detected by immunohistochemical stain.Periodic Acid-Schiff (PAS) and alcian blue stain,and Masson Trichrome stain were performed to evaluate the degree of airway remodeling.Results The differences of age and gender between two groups were not significant.Otherwise,the differences of FVC %pred,FEV1 %Pred,PC20,V75%pred,V50%pred and V25%pred were significant between two groups.The patients with asthma had submucosal gland hyperplasia,increased smooth muscle mass,subepithelial fibrosis and neovascularization,compared to subjects in the control group.The asthma groups showed increased expressions of VEGF and VEGFR1,more positively-stained cells of airway epithelial cells than the control group.The up-regulated expressions of VEGF and its receptor well correlated with the airway remodeling,air flow obstruction and airway hyperresponsiveness.After treatment with Budesonide-Formoterol for 6 months,the expressions of VEGF and VEGFR1 have been decreased,with decreased airway remodeling in patients with asthma.Conclusions The increased expressions of VEGF and its receptor are accompanied by increased number and size of vessels in asthmatic airway,as well as airway remodeling.Budesonide-Formoterol can decrease the expressions of vascular endothelial growth factor and receptor 1 with airway remodeling in asthma.The inhibition of VEGF and its receptor may be a good therapeutic strategy for asthma.