甲氟喹通过抑制巨噬细胞中的 KCNH2/Jak2/Stat3 信号通路改善肺纤维化。
Mefloquine improves pulmonary fibrosis by inhibiting the KCNH2/Jak2/Stat3 signaling pathway in macrophages.
机构信息
School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan, Anhui, China.
School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China.
出版信息
Biomed Pharmacother. 2024 Feb;171:116138. doi: 10.1016/j.biopha.2024.116138. Epub 2024 Jan 18.
Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease characterized by severe pulmonary fibrosis, for which there is an urgent need for effective therapeutic agents. Mefloquine (Mef) is a quinoline compound primarily used for the treatment of malaria. However, high doses (>25 mg/kg) may lead to side effects such as cardiotoxicity and psychiatric disorders. Here, we found that low-dose Mef (5 mg/kg) can safely and effectively treat IPF mice. Functionally, Mef can improve the pulmonary function of IPF mice (PIF, PEF, EF50, VT, MV, PENH), alleviating pulmonary inflammation and fibrosis by inhibiting macrophage activity. Mechanically, Mef probably regulates the Jak2/Stat3 signaling pathway by binding to the 492HIS site of Potassium voltage-gated channel subfamily H member 2 (KCNH2) protein in macrophages, inhibiting the secretion of macrophage inflammatory and fibrotic factors. In summary, Mef may inhibit macrophage activity by binding to KCNH2 protein, thereby slowing down the progress of IPF.
特发性肺纤维化（IPF）是一种危及生命的疾病，其特征是严重的肺纤维化，因此迫切需要有效的治疗药物。甲氟喹（Mef）是一种喹啉化合物，主要用于治疗疟疾。然而，高剂量（>25mg/kg）可能会导致副作用，如心脏毒性和精神障碍。在这里，我们发现低剂量 Mef（5mg/kg）可安全有效地治疗 IPF 小鼠。在功能上，Mef 可以改善 IPF 小鼠的肺功能（PIF、PEF、EF50、VT、MV、PENH），通过抑制巨噬细胞活性来减轻肺部炎症和纤维化。在机制上，Mef 可能通过与巨噬细胞中钾电压门控通道亚家族 H 成员 2（KCNH2）蛋白的 492HIS 位点结合来调节 Jak2/Stat3 信号通路，抑制巨噬细胞炎症和纤维化因子的分泌。总之，Mef 可能通过与 KCNH2 蛋白结合来抑制巨噬细胞活性，从而减缓 IPF 的进展。
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