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目的研究布地奈德(BUD)对慢性哮喘小鼠支气管上皮细胞的血清类黏蛋白1样蛋白3(ORMDL3),基质金属蛋白酶-9(MMP-9)表达的影响,及其对气道重塑的干预作用。方法应用BALB/C小鼠随机分为对照组、哮喘组、BUD组,用OVA(卵清蛋白)和氢氧化铝建立哮喘小鼠模型,为进一步了解布地奈德对气道重塑的干预机制,第21天BUD组小鼠在OVA激发前30min吸入布地奈德。12周后,用苏木精-伊红染色(HE staining)分析气道壁厚度改变,Masson染色观察气道胶原沉积,通过免疫组织化学染色法(immunohistochemistry staining),蛋白质印迹法(western blot),实时荧光定量PCR(real-time PCR)测定小鼠支气管上皮细胞ORMDL3,MMP-9的表达含量。结果 12周后,哮喘组和BUD组的气道壁厚度增加,胶原蛋白沉积,ORMDL3,MMP-9表达明显高于对照组,BUD组气道病理改变程度和ORMDL3,MMP-9的升高幅度均不及哮喘组。经相关性分析可发现,MMP-9表达增加与ORMDL3基因的表达上调具有相关性,并且二者的表达增高与气道壁厚度有明显相关性。结论布地奈德可能通过下调ORMDL3,MMP-9基因的表达,抑制慢性哮喘气道重塑进程。
Objective To investigate the effect of budesonide (BUD) on the expression of serum mucin-like protein 3 (ORMDL3) and matrix metalloproteinase-9 (MMP-9) in bronchial epithelial cells of chronic asthmatic mice and its effect on airway remodeling The role of intervention. Methods BALB / C mice were randomly divided into control group, asthma group and BUD group. Asthma mouse model was established by OVA and aluminum hydroxide. To further understand the intervention mechanism of budesonide on airway remodeling On day 21, BUD mice inhaled budesonide 30 min prior to challenge with OVA. Twelve weeks later, airway wall thickness was analyzed by hematoxylin and eosin staining, airway collagen deposition was observed by Masson staining, immunohistochemistry staining, western blot, Real-time PCR (real-time PCR) was used to detect the expression of ORMDL3 and MMP-9 in mouse bronchial epithelial cells. Results After 12 weeks, the airway wall thickness increased, the expression of collagen deposition, ORMDL3 and MMP-9 in the asthma group and the BUD group were significantly higher than those in the control group. The degree of airway pathological changes and the increase of ORMDL3 and MMP-9 in the BUD group Neither asthma group. Correlation analysis showed that the increase of MMP-9 expression was correlated with the up-regulation of ORMDL3 gene expression, and the expression of both was significantly correlated with the thickness of airway wall. Conclusion Budesonide may inhibit the process of airway remodeling in chronic asthma by down-regulating the expression of ORMDL3 and MMP-9.