Unrestrained inflammation provokes oxidative stress and contributes to the development of sepsis-induced acute lung injury (ALI). MicroRNA-326 (miR-326) is originally identified as an autoimmunity-associated microRNA, yet its role and potential molecular basis in sepsis-induced ALI remain unclear. Herein, we found that miR-326 was downregulated in murine lungs and macrophages upon lipopolysaccharide (LPS) stimulation. MiR-326 agomir prevented, whereas miR-326 antagomir exacerbated LPS-induced inflammation, oxidative stress and ALI in mice. Furthermore, we found that miR-326 suppressed LPS-induced inflammation and oxidative stress in macrophages via downregulating toll-like receptor (TLR4), and TLR4 inhibition abolished miR-326 antagomir-mediated deleterious effect in vivo and in vitro. Finally, we proved miR-326 agomir notably alleviated sepsis-induced ALI after cecal ligation and puncture surgery. Our data identified miR-326 as a potential therapeutic target for sepsis-induced ALI.

不受约束的炎症会激发氧化应激，并导致败血症诱发的急性肺损伤（ALI）的发展。MicroRNA-326（miR-326）最初被鉴定为自身免疫相关的microRNA，但其在脓毒症诱导的ALI中的作用和潜在的分子基础仍不清楚。在本文中，我们发现在脂多糖（LPS）刺激下，鼠肺和巨噬细胞中的miR-326被下调。MiR-326 agomir可以预防，而miR-326 antagomir可以加剧LPS诱导的小鼠炎症，氧化应激和ALI。此外，我们发现miR-326通过下调Toll样受体（TLR4）抑制巨噬细胞LPS诱导的炎症和氧化应激，而TLR4抑制则消除了miR-326 antagomir体内和体外介导的有害作用。最后，我们证明了miR-326 agomir可以在盲肠结扎和穿刺手术后明显减轻败血症诱导的ALI。我们的数据确定miR-326是脓毒症诱发的ALI的潜在治疗靶标。