Abstract：
Oxidative stress and endoplasmic reticulum stress (ERS) was associated with the development of asthma. Edaravone (EDA) plays a classical role to prevent the occurrence and development of oxidative stress-related diseases. Herein, we investigated the involvement and signaling pathway of EDA in asthma, with particular emphasis on its impact on type 2 innate lymphoid cells (ILC2) and CD4+T cells, and then further elucidated whether EDA could inhibit house dust mite (HDM)-induced allergic asthma by affecting oxidative stress and ERS. Mice received intraperitoneally injection of EDA (10 mg/kg, 30 mg/kg), dexamethasone (DEX) and N-acetylcysteine (NAC), with the latter two used as positive control drugs. DEX and high dose of EDA showed better therapeutic effects in alleviating airway inflammation and mucus secretion in mice, along with decreasing eosinophils and neutrophils in bronchoalveolar lavage fluid (BALF) than NAC. Further, the protein levels of IL-33 in lung tissues were inhibited by EDA, leading to reduced activation of ILC2s in the lung. EDA treatment alleviated the activation of CD4+ T cells in lung tissues of HDM-induced asthmatic mice and reduced Th2 cytokine secretion in BALF. ERS-related markers (p-eIF2α, IRE1α, CHOP, GRP78) were decreased after treatment of EDA compared to HDM group. Malondialdehyde (MDA), glutathione (GSH), hydrogen peroxide (H2O2), and superoxide dismutase (SOD) were detected to evaluate the oxidant stress in lung tissues. EDA showed a protective effect against oxidant stress. In conclusion, our findings demonstrated that EDA could suppress allergic airway inflammation by inhibiting oxidative stress and ERS, suggesting to serve as an adjunct medication for asthma in the future.
摘要：
氧化应激和内质网应激(ERS)与哮喘的发生发展有关。依达拉奉（EDA）在预防氧化应激相关疾病的发生和发展中起着经典的作用。在这里，我们调查了EDA在哮喘中的参与和信号通路，特别强调其对2型先天淋巴细胞（ILC2）和CD4+T细胞的影响，然后进一步阐明EDA是否可以通过影响氧化应激和ERS来抑制屋尘螨（HDM）引起的过敏性哮喘。小鼠腹腔注射EDA（10mg/kg，30mg/kg)，地塞米松（DEX）和N-乙酰半胱氨酸（NAC），后两者用作阳性对照药物。DEX和大剂量EDA对减轻小鼠气道炎症和黏液分泌有较好的治疗作用,与NAC相比，支气管肺泡灌洗液（BALF）中的嗜酸性粒细胞和中性粒细胞减少。Further,EDA抑制肺组织中IL-33的蛋白水平,导致肺中ILC2s的激活减少。EDA治疗减轻了HDM诱导的哮喘小鼠肺组织中CD4T细胞的活化，并减少了BALF中Th2细胞因子的分泌。ERS相关标志物(p-eIF2α，IRE1α,CHOP,与HDM组相比，EDA治疗后GRP78）降低。丙二醛(MDA),谷胱甘肽(GSH),过氧化氢(H2O2),并检测超氧化物歧化酶（SOD），以评估肺组织的氧化应激。EDA对氧化应激具有保护作用。总之,我们的发现表明，EDA可以通过抑制氧化应激和ERS来抑制过敏性气道炎症，建议将来作为哮喘的辅助药物。
