Acute lung injury (ALI) is a life-threatening disorder with high rates of morbidity and mortality. Up to now, there are still no effective drugs for its therapies due to the complexity of its etiology and pathogenesis. In this present study, we investigated the protective effect of Nervilifordin F (NF) on ALI induced by intestinal ischemia/reperfusion (II/R) and its related mechanism. Firstly, the ALI model rats were induced through II/R, and treated with NF. Then, the pathological and cytokine level changes in the lung tissue of ALI rats were evaluated by hematoxylin and eosin and enzyme-linked immunosorbent assay (ELISA). The related genes expression level of mammalian target of rapamycin (mTOR) pathway and inflammasome were measured by real-time quantitative polymerase chain reaction (RT-qPCR), western blot and immunohistochemistry. Finally, the NF-protein complexes were predicted by SYBYL-X 2.0. The results indicated that NF can significant reduces the levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and IL-1β, and inhibits the expression of inflammasome related genes (such as toll-like receptor 4 (TLR4), p65, NOD-like receptor protein 3 (NLRP3) and Caspase 1), thereby reduce inflammation in II/R-induced ALI rats. Moreover, NF can activate the expression of FK506 binding protein 25 (FKBP25) and down-regulate the expression of mTOR and p70 ribosomal protein S6 kinase 1 (p70S6K). In addition, molecular docking results showed that NF can be combined well with p70S6K, TLR4, mTOR and NLRP3, which further verified the inhibitory effect of NF on ALI inflammation. Therefore, the findings indicate that NF can alleviates II/R-induced inflammation of ALI rats by inhibiting inflammasome related genes and mTOR pathway, which expected to use as a potential drug for the treatment of ALI.

急性肺损伤（ALI）是威胁生命的疾病，发病率和死亡率很高。迄今为止，由于其病因和发病机理的复杂性，目前尚无有效的药物可用于其治疗。在本研究中，我们研究了神经营养素F（NF）对肠缺血/再灌注（II / R）诱导的ALI的保护作用及其相关机制。首先，通过II / R诱导ALI模型大鼠，并用NF处理。然后，通过苏木精和曙红和酶联免疫吸附试验（ELISA）评估ALI大鼠肺组织的病理学和细胞因子水平变化。通过实时定量聚合酶链反应（RT-qPCR），蛋白质印迹和免疫组化方法检测哺乳动物雷帕霉素靶标（mTOR）途径和炎症小体的相关基因表达水平。最后，SYBYL-X 2.0可预测NF-蛋白复合物。结果表明NF可以显着降低肿瘤坏死因子-α（TNF-α），白介素（IL）-6和IL-1β的水平，并抑制炎性体相关基因（例如toll样受体4（ TLR4），p65，NOD样受体蛋白3（NLRP3）和Caspase 1），从而减轻II / R诱导的ALI大鼠的炎症。此外，NF可以激活FK506结合蛋白25（FKBP25）的表达，并下调mTOR和p70核糖体蛋白S6激酶1（p70S6K）的表达。另外，分子对接结果表明NF可以与p70S6K，TLR4，mTOR和NLRP3良好结合，进一步证实了NF对ALI炎症的抑制作用。因此，