黄芪甲苷对慢性哮喘模型小鼠气道重塑的影响

Effects of Astragaloside Ⅳ on airway remodeling in a murine model of chronic asthma

目的观察黄芪甲苷对慢性哮喘小鼠模型气道重塑的影响。方法 48只BALB/c小鼠按随机原则分成正常对照组、哮喘组、黄芪甲苷组、布地奈德组,每组12只。卵蛋白致敏,气道激发8周。黄芪甲苷组和布地奈德组分别给予黄芪甲苷溶液(50 mg·kg-1)灌胃,布地奈德混悬液(8 ml)雾化,每日1次,共8周。末次激发24 h后,每组取6只小鼠评价呼气阻力,支气管肺泡灌洗液(BALF)观察炎症细胞计数,HE染色和Masson染色观察气道炎症和上皮下纤维化情况,ELISA检测BALF中血管内皮生长因子(VEGF)水平,免疫组织化学检测α-平滑肌肌动蛋白(α-SMA)和VEGF蛋白表达。结果黄芪甲苷能够明显抑制慢性哮喘小鼠模型的气道炎症、气道高反应性和气道重塑。黄芪甲苷治疗后哮喘小鼠BALF中VEGF含量明显降低,哮喘小鼠肺组织高表达的α-SMA和VEGF蛋白水平也明显降低。结论黄芪甲苷能够抑制慢性哮喘小鼠模型的气道重塑,其机制可能通过抑制VEGF表达而实现。

Aim To observe the effects of Astragaloside Ⅳ on the airway remodeling in a murine model of chronic asthma.Methods 48 BALB/c mice were randomly divided into 4 groups,namely Control group,Asthma group（OVA group）,Astragaloside Ⅳ group and Budesonide group with 12 mice in each group.BALB/c mice sensitized to ovalbumin（OVA） were chronically challenged with aerosolized OVA for eight weeks.Mice in the Astragaloside Ⅳ group were intragastrically administered with Astragaloside Ⅳ（50 mg·kg-1） daily for 8 consecutive weeks.Mice in the Budesonide group were exposed to an aerosol of budesonide（8 ml） daily for 8 consecutive weeks.24 hours after the last OVA challenge,pulmonary functions were measured to evaluate the resistance of expiration in 6 mice of each group.Cells in BAL fluid（BALF） were counted.The sections were stained with either hematoxylin eosin to assess the inflammatory cell infiltrates,and Masson′s trichrome to determine subepithelial fibrosis in the lungs.The levels of VEGF in BALF were measured by ELISA.The expression of α-SMA and VEGF protein in lungs was detected by immunohistochemistry.Results Treatment with Astragaloside Ⅳ markedly inhibited the airway inflammation,airway hyperresponsiveness（AHR） and remodeling.Astragaloside Ⅳ significantly decreased the level of VEGF in BLAF.In addition,Astragaloside Ⅳ obviously attenuated the protein expression of α-SMA and VEGF in lungs.Conclusions Astragaloside Ⅳ can suppress the progression of airway remodeling in a murine model of chronic asthma.Partly,the effects might be due to inhibition of the expression of VEGF.