Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Sci Rep. 2017 Mar 7;7(1):99. doi: 10.1038/s41598-017-00103-0.
Recently, a serial of studies have demonstrated that lipid mediators derived from Omega-3 fatty acid docosahexaenoic acid have pro-resolving or anti-inflammatory effects in many inflammatory diseases. Here, we sought to evaluate whether Protectin DX (PDX, an isomer of Protecin D1), a newly identified lipid mediator, could protect mice against sepsis and explore the underling mechanism. Animal model of sepsis was established by cecum ligation and puncture (CLP). We found that PDX increased overall survival rate within eight days and attenuated multiple organ injury in septic mice. In addition, PDX reduced pro-inflammatory cytokines and bacterial load 24 h after CLP. Moreover, PDX promoted phagocytosis of peritoneal macrophages and increased the percentage of M2 macrophages in peritoneum of septic mice. In vitro, M2 macrophage markers (Arg1 and Ym1) and its transcriptional regulator (peroxisome proliferator-activated receptor-γ, PPAR-γ) were upregulated in Raw264.7 macrophages challenged with PDX. GW9662 (a PPAR-γ inhibitor) and PPAR-γ siRNA abrogated the induction of Arg1 and Ym1 by PDX in Raw264.7 cells. Taken together, our results suggest that PDX is able to promote M2 polarization, enhance phagocytosis activity of macrophage and accelerate resolution of inflammation, finally leading to increased survival rate of septic mice.
最近，一系列研究表明，源自 ω-3 脂肪酸二十二碳六烯酸的脂质介质在许多炎症性疾病中具有促解决或抗炎作用。在这里，我们试图评估新发现的脂质介质保护素 DX（PDX，保护素 D1 的异构体）是否可以保护小鼠免受败血症的影响，并探讨其潜在机制。通过盲肠结扎和穿刺（CLP）建立败血症动物模型。我们发现 PDX 在 8 天内提高了总生存率，并减轻了败血症小鼠的多器官损伤。此外，PDX 在 CLP 后 24 小时降低了促炎细胞因子和细菌负荷。此外，PDX 促进了腹腔巨噬细胞的吞噬作用，并增加了败血症小鼠腹腔内 M2 巨噬细胞的百分比。在体外，PDX 刺激 Raw264.7 巨噬细胞后，M2 巨噬细胞标志物（Arg1 和 Ym1）及其转录调节剂（过氧化物酶体增殖物激活受体-γ，PPAR-γ）上调。GW9662（PPAR-γ 抑制剂）和 PPAR-γ siRNA 阻断了 PDX 在 Raw264.7 细胞中诱导 Arg1 和 Ym1 的作用。总之，我们的研究结果表明，PDX 能够促进 M2 极化，增强巨噬细胞的吞噬活性，并加速炎症消退，最终导致败血症小鼠生存率提高。
