Department of Anesthesiology, Zhongnan Hospital of Wuhan University, 430071 Wuhan, Hubei, People's Republic of China.
Department of Anesthesiology, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, People's Republic of China.
Cell Signal. 2020 May;69:109556. doi: 10.1016/j.cellsig.2020.109556. Epub 2020 Feb 4.
Septic lung injury is one of main causes of high mortality in severe patients. Inhibition of excessive inflammatory response is considered as an effective strategy for septic lung injury. Previous studies have shown that cannabinoid receptor 2 (CB2), a G protein-coupled receptor, play an important role in immunosuppression. Whether CB2 can be used as a therapeutic target for septic lung injury is unclear. The aim of this study is to explore the role of CB2 in sepsis and its potential mechanism. In this study, treatment with HU308, a specific agonist of CB2, could reduce lung pathological injury, decrease the level of inflammatory cytokines and strengthen the expression of autophagy-related gene after cecal ligation puncture (CLP)-induced sepsis in mice. Similar results were obtained in RAW264.7 macrophages after LPS treatment. Furthermore, the effect of HU308 could be blocked by autophagy blocker 3-MA in vivo and in vitro. These results suggest that CB2 serves as a protective target for septic lung injury by decreasing inflammatory factors, which is associated with the enhancement of autophagy.
脓毒症性肺损伤是重症患者高死亡率的主要原因之一。抑制过度炎症反应被认为是脓毒症性肺损伤的有效策略。先前的研究表明，大麻素受体 2（CB2）是一种 G 蛋白偶联受体，在免疫抑制中发挥重要作用。CB2 是否可以作为脓毒症性肺损伤的治疗靶点尚不清楚。本研究旨在探讨 CB2 在脓毒症中的作用及其潜在机制。在这项研究中，用 CB2 的特异性激动剂 HU308 治疗盲肠结扎穿刺（CLP）诱导的脓毒症小鼠可以减轻肺组织病理损伤，降低炎症细胞因子水平，并增强自噬相关基因的表达。在 LPS 处理后的 RAW264.7 巨噬细胞中也得到了类似的结果。此外，HU308 的作用可以在体内和体外被自噬抑制剂 3-MA 阻断。这些结果表明，CB2 通过降低炎症因子来减轻脓毒症性肺损伤，这与自噬的增强有关。
