Department of Anesthesiology, Critical Care and Pain Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Western Road, Wenzhou, Zhejiang Province 325027, PR China.
Department of Pathophysiology, Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, PR China.
Life Sci. 2018 Jun 1;202:89-97. doi: 10.1016/j.lfs.2018.04.005. Epub 2018 Apr 5.
Endotoxin induced acute lung injury (ALI) is a critical complication of some clinical illnesses. Endothelial cell dysfunction and excessive pro-inflammation cytokine release are pivotal to the injury of alveolar-capillary membrane which is the typical characteristic of endotoxic lung injury. As a potential marker of endothelial cells, endocan plays an important role in many endothelial-dependent pathophysiological diseases. We speculated that endocan have anti-inflammatory property in ALI. Here, we investigated the role of endocan in LPS-induced ALI.
Mice were randomly divided into 4 groups. LPS were used to construct ALI mice model by aerosolization for 20 min. Endocan was intraperitoneal injected at 30 min before LPS exposure. Levels of TNF-α, IFN-γ, IL-1β, IL-6 and MPO activities were detected by indicated ELISA. Cell apoptotic rate was determined by Annexin V/PI kit, ROS level and MPTP were detected by DCFH-DA and JC-1 kit, respectively. Seahorse XF96 was applied to evaluate the alteration of OCR and ECAR. Western blot and qRT-PCR were used to detect indicated molecules.
Endocan effectively decreased TNF-α, IFN-γ, IL-1β, and IL-6 levels as well as relieved pulmonary epithelium cell apoptosis caused by LPS exposure. Endocan significantly reversed LPS induced UPR and promoted cell metabolism reprogramming which were crucial for the protective characteristic of endocan in ALI mice model.
The above findings suggested endocan could significantly suppress inflammatory response in ALI model through attenuating UPR associated apoptosis and switch cellular bioenergetics, indicating endocan could be considered as a promising compound against LPS induced ALI.
内毒素诱导的急性肺损伤（ALI）是某些临床疾病的严重并发症。内皮细胞功能障碍和过度促炎细胞因子释放是肺泡-毛细血管膜损伤的关键，这是内毒素性肺损伤的典型特征。作为内皮细胞的潜在标志物，内脂素在许多内皮依赖性病理生理疾病中发挥重要作用。我们推测内脂素在 ALI 中有抗炎作用。在这里，我们研究了内脂素在 LPS 诱导的 ALI 中的作用。
小鼠随机分为 4 组。通过雾化 20 分钟构建 LPS 诱导的 ALI 小鼠模型。LPS 暴露前 30 分钟经腹腔注射内脂素。通过指示性 ELISA 检测 TNF-α、IFN-γ、IL-1β、IL-6 和 MPO 活性水平。通过 Annexin V/PI 试剂盒测定细胞凋亡率，通过 DCFH-DA 和 JC-1 试剂盒分别检测 ROS 水平和 MPTP，使用 Seahorse XF96 评估 OCR 和 ECAR 的变化。Western blot 和 qRT-PCR 用于检测指示分子。
内脂素有效降低了 LPS 暴露引起的 TNF-α、IFN-γ、IL-1β 和 IL-6 水平，并缓解了肺上皮细胞凋亡。内脂素显著逆转了 LPS 诱导的 UPR，并促进了细胞代谢重编程，这对内脂素在 ALI 小鼠模型中的保护作用至关重要。
上述发现表明，内脂素通过抑制 UPR 相关的细胞凋亡和改变细胞代谢，显著抑制 ALI 模型中的炎症反应，表明内脂素可被视为一种有前途的抗 LPS 诱导的 ALI 化合物。
