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Cannabinoid receptor 2 activation alleviates septic lung injury by promoting autophagy via inhibition of inflammatory mediator release

机译:大麻素受体2激活通过抑制炎症介质释放来促进自噬来减轻脓肺损伤

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摘要

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.
机译:脓毒症肺损伤是严重患者死亡率高的主要原因之一。抑制过度炎症反应被认为是脓毒肺损伤的有效策略。以前的研究表明,大麻素受体2(CB2),G蛋白偶联受体,在免疫抑制中起重要作用。 CB2是否可以用作化粪池肺损伤的治疗靶标尚不清楚。本研究的目的是探讨CB2在败血症中的作用及其潜在机制。在本研究中,用HU308治疗CB2的特异性激动剂可以降低肺部病理损伤,降低炎症细胞因子的水平,并加强盲肠结扎穿刺(CLP)诱导小鼠脓毒症后自噬相关基因的表达。在LPS处理后Raw264.7巨噬细胞中获得了类似的结果。此外,HU308的效果可以通过体内和体内的自噬阻滞剂3-mA阻断。这些结果表明CB2通过降低炎症因素,作为脓毒症肺损伤的保护靶,这与自噬的增强有关。

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