Department of Anesthesiology, Peking Union Medical College Hospital, No. 1 Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China.
Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 33# Shijingshan District, Beijing, 100144, China.
Inflammation. 2018 Jun;41(3):914-923. doi: 10.1007/s10753-018-0746-2.
Propofol, an intravenous anesthetic agent widely used in clinical practice, is the preferred anesthetic for asthmatic patients. This study was designed to determine the protective effect and underlying mechanisms of propofol on airway inflammation in a mast cell-dependent mouse model of allergic asthma. Mice were sensitized by ovalbumin (OVA) without alum and challenged with OVA three times. Propofol was given intraperitoneally 0.5 h prior to OVA challenge. The inflammatory cell count and production of cytokines in the bronchoalveolar lavage fluid (BALF) were detected. The changes of lung histology and key molecules of the toll-like receptor 4 (TLR4)/reactive oxygen species (ROS)/NF-κB signaling pathway were also measured. The results showed that propofol significantly decreased the number of eosinophils and the levels of IL-4, IL-5, IL-6, IL-13, and TNF-α in BALF. Furthermore, propofol significantly attenuated airway inflammation, as characterized by fewer infiltrating inflammatory cells and decreased mucus production and goblet cell hyperplasia. Meanwhile, the expression of TLR4, and its downstream signaling adaptor molecules--myeloid differentiation factor 88 (MyD88) and NF-κB, were inhibited by propofol. The hydrogen peroxide and methane dicarboxylic aldehyde levels were decreased by propofol, and the superoxide dismutase activity was increased in propofol treatment group. These findings indicate that propofol may attenuate airway inflammation by inhibiting the TLR4/MyD88/ROS/NF-κB signaling pathway in a mast cell-dependent mouse model of allergic asthma.
丙泊酚是一种在临床实践中广泛应用的静脉麻醉剂，是哮喘患者首选的麻醉剂。本研究旨在确定丙泊酚对肥大细胞依赖性变应性哮喘小鼠模型气道炎症的保护作用及其潜在机制。通过卵清蛋白（OVA）致敏且无明矾，以及 OVA 三次激发来致敏小鼠。在 OVA 激发前 0.5 h 给予丙泊酚腹腔内给药。检测支气管肺泡灌洗液（BALF）中的炎症细胞计数和细胞因子的产生。还测量了肺组织学变化和 toll 样受体 4（TLR4）/活性氧（ROS）/核因子-κB（NF-κB）信号通路的关键分子的变化。结果表明，丙泊酚可显著降低 BALF 中嗜酸性粒细胞的数量和白细胞介素 4（IL-4）、白细胞介素 5（IL-5）、白细胞介素 6（IL-6）、白细胞介素 13（IL-13）和肿瘤坏死因子-α（TNF-α）的水平。此外，丙泊酚显著减轻气道炎症，表现为浸润性炎症细胞减少、粘液产生和杯状细胞增生减少。同时，丙泊酚抑制了 TLR4 及其下游信号接头分子髓样分化因子 88（MyD88）和 NF-κB 的表达。丙泊酚降低了过氧化氢和甲烷二羧酸醛的水平，增加了超氧化物歧化酶的活性。这些发现表明，丙泊酚可能通过抑制肥大细胞依赖性变应性哮喘小鼠模型中的 TLR4/MyD88/ROS/NF-κB 信号通路来减轻气道炎症。
