Asthma is characterized by inflammation, pulmonary remodeling and bronchial hyperresponsiveness. We have previously shown that treatment with angiotensin-(1-7) [Ang-(1-7)] promotes resolution of eosinophilic inflammation and prevents chronic allergic lung inflammation. Here, we evaluated the effect of treatment with the inclusion compound of Ang-(1-7) in hydroxypropyl β-cyclodextrin (HPβCD) given by inhalation on pulmonary remodeling in an ovalbumin (OVA)-induced chronic allergic lung inflammation. Mice were sensitized to ovalbumin (OVA; 4 injections over 42 days, 14 days apart) and were challenged 3 times per week, for 4 weeks (days 21–46). After the 2nd week of challenge, mice were treated with Ang-(1-7) by inhalation (4.5 μg of Ang-(1-7) included in 6.9 μg of HPβCD for 14 days, i.e. days 35–48). Mice were killed 72 h after the last challenge and blood, bronchoalveolar lavage fluid (BALF) and lungs were collected. Histology and morphometric analysis were performed in the lung. Metalloproteinase (MMP)-9 and MMP-12 expression and activity, IL-5, CCL11 in the lung and plasma IgE were measured. After 2 weeks of OVA challenge there was an increase in plasma IgE and in inflammatory cells infiltration in the lung of asthmatic mice. Treatment with inhaled administration of Ang-(1-7)/HPβCD for 14 days reduced eosinophils, IL5, CCL11 in the lung and plasma IgE. Treatment of asthmatic mice with Ang-(1-7)/HPβCD by inhalation reversed pulmonary remodeling by reducing collagen deposition and MMP-9 and MMP-12 expression and activity. These results show for the first time that treatment by inhalation with Ang-(1-7) can reverse an installed asthma, inhibiting pulmonary inflammation and remodeling.

哮喘的特征在于炎症、肺重塑和支气管高反应性。我们之前已经表明，用血管紧张素-(1-7) [Ang-(1-7)] 进行治疗可促进嗜酸性粒细胞炎症的消退并预防慢性过敏性肺部炎症。在这里，我们评估了通过吸入给予的羟丙基 β-环糊精 (HPβCD) 中的 Ang-(1-7) 包合物治疗对卵清蛋白 (OVA) 诱导的慢性过敏性肺部炎症的肺重塑的影响。小鼠对卵清蛋白（OVA；在 42 天内注射 4 次，相隔 14 天）敏感，并且每周攻击 3 次，持续 4 周（第 21-46 天）。在第 2 周攻击后，通过吸入用 Ang-(1-7) 处理小鼠（4.5 μg Ang-(1-7) 包含在 6.9 μg HPβCD 中，持续 14 天，即第 35-48 天）。在最后一次攻击后 72 小时处死小鼠并收集血液、支气管肺泡灌洗液 (BALF) 和肺。在肺中进行组织学和形态计量学分析。测量了金属蛋白酶 (MMP)-9 和 MMP-12 的表达和活性、IL-5、肺和血浆 IgE 中的 CCL11。OVA 攻击 2 周后，哮喘小鼠肺中的血浆 IgE 和炎症细胞浸润增加。吸入 Ang-(1-7)/HPβCD 治疗 14 天可减少肺中的嗜酸性粒细胞、IL5、CCL11 和血浆 IgE。用 Ang-(1-7)/HPβCD 通过吸入治疗哮喘小鼠通过减少胶原沉积和 MMP-9 和 MMP-12 表达和活性逆转肺重塑。这些结果首次表明，通过吸入 Ang-(1-7) 进行治疗可以逆转已安装的哮喘，