Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui, China.
School of Basic Medical Sciences, Anhui Medical University, Meishan Road 81, Hefei, Anhui, China.
Inflammation. 2019 Jun;42(3):1015-1022. doi: 10.1007/s10753-019-00963-w.
Asthma is characterized by chronic airway inflammation, which is the underlying cause of airway remodeling featured by goblet cell hyperplasia, subepithelial fibrosis, and proliferation of smooth muscle. Sevoflurane has been used to treat life-threatening asthma and our previous study shows that sevoflurane inhibits acute lung inflammation in ovalbumin (OVA)-induced allergic mice. However, the effect of sevoflurane on airway remodeling in the context of chronic airway inflammation and the underlying mechanism are still unknown. Here, female C57BL/6 mice were used to establish chronic airway inflammation model. Hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and Sirius red (SR) staining were used to evaluate airway remodeling. Protein levels of α-SMA, VEGF, and TGF-β1 in lung tissues were detected by western blotting analyses and immunohistochemistry staining. Results showed that inhalation of sevoflurane inhibited chronic airway inflammation including inflammatory cell infiltration and pro-inflammatory cytokine production in BALF of the OVA-challenged mice. Meanwhile, sevoflurane suppressed airway thickening, goblet cell hyperplasia, smooth muscle hyperplasia, collagen deposition, and fiber hyperplasia in the lung tissues of the mice with airway remodeling. Most notably, sevoflurane inhibited the OVA-induced expressions of VEGF and TGF-β1. These results suggested that sevoflurane effectively inhibits airway remodeling in mouse model of chronic airway inflammation, which may be due to the downregulation of VEGF and TGF-β1in lung tissues. Therefore, our results indicate a potential role of sevoflurane in inhibiting airway remodeling besides its known suppression effect on airway inflammation, and support the use of sevoflurane in treating severe asthma in ICU.
哮喘的特征是慢性气道炎症，这是气道重塑的根本原因，其特征是杯状细胞增生、上皮下纤维化和平滑肌增殖。七氟醚已被用于治疗危及生命的哮喘，我们之前的研究表明，七氟醚抑制卵清蛋白（OVA）诱导的过敏性小鼠的急性肺炎症。然而，七氟醚在慢性气道炎症背景下对气道重塑的影响及其潜在机制仍不清楚。在这里，我们使用雌性 C57BL/6 小鼠建立了慢性气道炎症模型。使用苏木精和伊红（H&E）、过碘酸-希夫（PAS）和天狼星红（SR）染色来评估气道重塑。通过 Western blot 分析和免疫组织化学染色检测肺组织中 α-SMA、VEGF 和 TGF-β1 的蛋白水平。结果表明，吸入七氟醚抑制了 OVA 挑战小鼠的慢性气道炎症，包括炎症细胞浸润和 BALF 中促炎细胞因子的产生。同时，七氟醚抑制了气道重塑小鼠气道变厚、杯状细胞增生、平滑肌增生、胶原沉积和纤维增生。值得注意的是，七氟醚抑制了 OVA 诱导的 VEGF 和 TGF-β1 的表达。这些结果表明，七氟醚有效地抑制了慢性气道炎症小鼠模型中的气道重塑，这可能是由于肺组织中 VEGF 和 TGF-β1 的下调。因此，我们的结果表明，除了已知的抑制气道炎症作用外，七氟醚在抑制气道重塑方面具有潜在作用，并支持在 ICU 中使用七氟醚治疗严重哮喘。
