目的:急性肺损伤(ALI)是一种以炎性细胞浸润和肺上皮损伤为特征的危及生命的肺部疾病。淫羊藿苷II(ICSII),淫羊藿的主要活性成分之一,表现出抗炎和免疫调节作用。然而,ICSII在ALI中的作用和机制尚不清楚.本研究的目的是研究ICSII在ALI中的药理作用和潜在机制。
方法:中性粒细胞样细胞模型,人外周血中性粒细胞,采用脂多糖(LPS)诱导的ALI小鼠模型。RT-qPCR和Western印迹测定基因和蛋白质表达水平。通过免疫荧光分析蛋白质分布和定量。
结果:ICSII显著减轻了肺组织病理学损伤,水肿,和炎症细胞浸润,并减少ALI中的促炎细胞因子。中性粒细胞的过度激活导致ALI小鼠中NETs的大量产生,ICSII的管理缓解了这一过程。体内和体外研究发现,ICSII可以通过靶向中性粒细胞C-X-C趋化因子受体4型(CXCR4)来减少NET的形成。进一步的数据显示,ICSII减少了dsDNA的过度生产,NET相关组件,从而抑制cGAS/STING/NF-κB信号通路激活和肺上皮细胞炎症介质释放。
结论:这项研究表明,ICSII可能通过调节炎症反应来减轻LPS诱导的ALI,表明其作为ALI治疗的治疗剂的潜力。
OBJECTIVE: Acute lung injury (ALI) is a life-threatening lung disease characterized by inflammatory cell infiltration and lung epithelial injury. Icariside II (ICS II), one of the main active ingredients of Herba Epimedii, exhibits anti-inflammatory and immunomodulatory effects. However, the effect and mechanism of ICS II in ALI remain unclear. The purpose of the current study was to investigate the pharmacological effect and underlying mechanism of ICS II in ALI.
METHODS: Models of neutrophil-like cells, human peripheral blood neutrophils, and lipopolysaccharide (LPS)-induced ALI mouse model were utilized. RT-qPCR and Western blotting determined the gene and protein expression levels. Protein distribution and quantification were analyzed by immunofluorescence.
RESULTS: ICS II significantly reduced lung histopathological damage, edema, and inflammatory cell infiltration, and it reduced pro-inflammatory cytokines in ALI. There is an excessive activation of neutrophils leading to a significant production of NETs in ALI mice, a process mitigated by the administration of ICS II. In vivo and in vitro studies found that ICS II could decrease NET formation by targeting neutrophil C-X-C chemokine receptor type 4 (CXCR4). Further data showed that ICS II reduces the overproduction of dsDNA, a NETs-related component, thereby suppressing cGAS/STING/NF-κB signalling pathway activation and inflammatory mediators release in lung epithelial cells.
CONCLUSIONS: This study suggested that ICS II may alleviate LPS-induced ALI by modulating the inflammatory response, indicating its potential as a therapeutic agent for ALI treatment.