吸入重组人表皮生长因子对大鼠哮喘模型影响

Effects of inhaled recombinant human epidermal growth factor on rat asthma model

目的观察吸入重组人表皮生长因子是否可以促进哮喘时损伤上皮的修复,并对气道炎症和气道重塑产生影响。方法应用卵蛋白致敏和激发的方法制作SD大鼠慢性哮喘模型。采用病理学和免疫组织化学等方法比较吸入重组人表皮生长因子(rhEGF)组和吸入布地奈得(BUD)组与哮喘模型组在哮喘样症状、BALF中细胞数、肺病理形态学、气道周围浸润的嗜酸细胞数、上皮下纤维连接蛋白(FN)沉积以及支气管上皮增殖指标BrdU、炎性因子ICAM_l、RANTES和生长因子EGF、TGF_βl表达的不同。结果与模型组相比,rhEGF组哮喘样症状评分下降、BALF中炎性细胞和上皮细胞数目减少,气道周围浸润的嗜酸细胞数减少,上皮下FN沉积减少,上皮表达BrdU的阳性细胞数增加,上皮ICAM_l、RANTES和TGF_βl的表达下调,上皮EGF表达上调。与模型组相比,BUD组支气管上皮BrdU、EGF和TGF_βl的表达差异无显著性。结论吸入rhEGF能促进损伤上皮的修复和增殖,恢复上皮形态和结构的完整性,对哮喘的气道炎症和气道重塑有部分抑制作用。

Objective To investigate the effects of inhaled recombinant human epidermal growth factor(rhEGF)on the repair of damaged epithelium and inhibition of airway inflammation and remodeling.Methods The chronic asthmatic model of SD rats was established with ovalbumin sensitization and chal-lenge method.Thirty-two SD rats were divided into three groups:rhEGF group in which rats inhaled rhEGF,BUD group in which rats inhaled budesonide(BUD)and asthma model group.Asthma-like symptom scores,cell counting in bronchoalveolar fluid lavage,lung pathological changes,number of eosinophils infiltrating around airways,deposition of fibronectin(FN)under epithelium and the expression of BrdU,ICAM-1,RANTES,TGF-β1and EGF in bronchial epithelium were determined.The differences in these four groups were compared.Results In comparison with asthma model group,asthma-like symptom scores,the number of inflammatory and epithelial cells in BALF,the number of esoinophils around large and middle airways,the expressions of ICAM-1,RANTES,TGF-β1in epithelia and FN the deposition of FN under epithelium all de-creased significantly whereas the Brdu positive cells and expression of EGF in epithelium increased signifi-cantly in rhEGF group.But no significant difference could be found between BUD group and asthma model group in expression of BrdU,EGF and TGF-β1in epithelium.Conclusions Inhaled rhEGF can promote the repair and proliferation of damaged epithelium,restore the integrity of epithelium structure and partly in-hibit airway inflammation and remodeling in rats with asthma.