Sepsis-induced acute lung injury (ALI) is a life-threatening medical condition with high mortality and morbidity in the critical care units. Though, it was commonly accepted that inflammation and apoptosis of lung epithelial cells played an essential role in the pathogenesis of ALI, the underlying mechanism remain unknown. In our study, we found that LPS-induced cell apoptosis could be counteracted by elevated cell autophagy. In LPS-treated MLE-12 cells, suppression of autophagy via 3-MA could aggravate LPS-induced apoptosis, while activation of autophagy via Rapamycin could effectively impair the apoptosis of MLE-12 cells induced by LPS. In order to further discover the molecular regulation mechanism between apoptosis and autophagy in LPS-treated MLE-12 cells, we demonstrated that autophagy could induced the expression of Nrf2, followed with the decrease of p-p65. Targeted inhibition of Nrf2 could induce enlarged cell apoptosis via increasing the level of p-p65. In addition, we demonstrated that ginsenoside Rg1 protected MLE-12 cells from LPS-induced apoptosis via augmenting autophagy and inducing the expression of Nrf2. Our data implicates that activation of autophagy and Nrf2 by ginsenoside Rg1 may provide a preventive and therapeutic strategy for ALI.

脓毒症引起的急性肺损伤 (ALI) 是一种危及生命的疾病，在重症监护病房中死亡率和发病率都很高。尽管普遍认为肺上皮细胞的炎症和凋亡在 ALI 的发病机制中起重要作用，但其潜在机制仍不清楚。在我们的研究中，我们发现升高的细胞自噬可以抵消 LPS 诱导的细胞凋亡。在 LPS 处理的 MLE-12 细胞中，通过 3-MA 抑制自噬可以加剧 LPS 诱导的细胞凋亡，而通过雷帕霉素激活自噬可以有效地损害 LPS 诱导的 MLE-12 细胞的凋亡。为了进一步发现 LPS 处理的 MLE-12 细胞凋亡和自噬之间的分子调控机制，我们证明自噬可以诱导 Nrf2 的表达，随着 p-p65 的减少。靶向抑制 Nrf2 可通过增加 p-p65 水平诱导细胞凋亡扩大。此外，我们证明人参皂苷 Rg1 通过增强自噬和诱导 Nrf2 的表达来保护 MLE-12 细胞免受 LPS 诱导的细胞凋亡。我们的数据表明，人参皂苷 Rg1 激活自噬和 Nrf2 可能为 ALI 提供预防和治疗策略。