Previous reports have demonstrated that the newly identified lipid mediator protectin DX (PDX) could effectively attenuate multiple organ injuries in sepsis. The aim of our study was to clarify whether PDX could improve acute lung injury (ALI) induced by sepsis and elucidate the relevant potential mechanism. After inducing sepsis by the cecal ligation and puncture approach, mice were treated with a high or low dose of PDX. Pathological changes in the pulmonary tissue were analyzed by hematoxylin-eosin staining, and lung injury score was evaluated. Lung permeability and edema were assessed by lung wet/dry ratio, and protein and cellular load of the bronchoalveolar lavage fluid (BALF). Inflammatory cytokine levels in BALF were measured by ELISA and the expression of PPARγ in the lung tissue was analyzed by immunoblotting. The results suggested that PDX could diminish the inflammatory response in lung tissue after sepsis by upregulating PPARγ and inhibiting the phosphorylation and activation of NF-κB p65. PDX treatment lowered the levels of pro-inflammation cytokines IL-1β, IL-6, TNF-α, and MCP-1, and the levels of anti-inflammatory cytokine IL-10 was increased in the BALF. It also improved lung permeability and reduced lung injury. Furthermore, the protective effect of PDX on lung tissue could be reversed by GW9662, a specific PPAR-γ antagonist. Taken together, our study indicated that PDX could ameliorate the inflammatory response in ALI by activating the PPARγ/NF-κB pathway in a mouse model of sepsis.

先前的报告表明，新发现的脂质介质保护素 DX (PDX) 可以有效减轻脓毒症中的多器官损伤。我们研究的目的是阐明 PDX 是否可以改善败血症诱导的急性肺损伤 (ALI) 并阐明相关的潜在机制。通过盲肠结扎和穿刺方法诱导败血症后，用高剂量或低剂量的 PDX 治疗小鼠。苏木精-伊红染色分析肺组织病理变化，评估肺损伤评分。通过肺湿/干比以及支气管肺泡灌洗液 (BALF) 的蛋白质和细胞负荷来评估肺通透性和水肿。通过ELISA测量BALF中的炎性细胞因子水平，并通过免疫印迹分析肺组织中PPARγ的表达。结果表明，PDX可以通过上调PPARγ和抑制NF-κB p65的磷酸化和活化来减轻脓毒症后肺组织的炎症反应。PDX 治疗降低了促炎细胞因子 IL-1β、IL-6、TNF-α 和 MCP-1 的水平，而 BALF 中抗炎细胞因子 IL-10 的水平增加。它还可以改善肺通透性并减少肺损伤。此外，PDX 对肺组织的保护作用可以被 GW9662（一种特定的 PPAR-γ 拮抗剂）逆转。总之，我们的研究表明，PDX 可以通过激活脓毒症小鼠模型中的 PPARγ/NF-κB 通路来改善 ALI 的炎症反应。PDX 治疗降低了促炎细胞因子 IL-1β、IL-6、TNF-α 和 MCP-1 的水平，而 BALF 中抗炎细胞因子 IL-10 的水平增加。它还可以改善肺通透性并减少肺损伤。此外，PDX 对肺组织的保护作用可以被 GW9662（一种特定的 PPAR-γ 拮抗剂）逆转。总之，我们的研究表明，PDX 可以通过激活脓毒症小鼠模型中的 PPARγ/NF-κB 通路来改善 ALI 的炎症反应。PDX 治疗降低了促炎细胞因子 IL-1β、IL-6、TNF-α 和 MCP-1 的水平，而 BALF 中抗炎细胞因子 IL-10 的水平增加。它还可以改善肺通透性并减少肺损伤。此外，PDX 对肺组织的保护作用可以被 GW9662（一种特定的 PPAR-γ 拮抗剂）逆转。总之，我们的研究表明，PDX 可以通过激活脓毒症小鼠模型中的 PPARγ/NF-κB 通路来改善 ALI 的炎症反应。