Herbacetin attenuates lipopolysaccharide-induced inflammatory lung injury in mice by inhibiting Fth1hi neutrophil aggregation and accelerating its clearance

The aim of this study was to systematically investigate the protective effect of Herbacetin (Her) against lipopolysaccharide (LPS)-induced inflammatory lung injury and its related mechanisms. Firstly, a mouse model of inflammatory lung injury was successfully constructed by intratracheal drip injection of LPS, and its protective effect on mice with inflammatory lung injury was evaluated by observing the overall lung tissue morphology changes, lung histopathological injury, lung wet-to-dry weight ratio, lung organ coefficients, total proteins, and inflammatory factor contents. The results showed that administration of Her treatment improved LPS-induced lung histopathological injury, reduced lung tissue edema, decreased the content of pro-inflammatory factors TNF-α, IL-6 and IL-1β, and reduced the number of inflammatory cells. Meanwhile, our results also showed that two neutrophil populations (Fth1hi Neu and Prok2hi Neu) in two different locations existed in the lung tissues of mice with LPS-induced inflammatory lung injury, and that LPS stimulation promoted the aggregation of Fth1hi Neu and the release of pro-inflammatory factors in the lung tissues, which was accompanied by a decrease in the content of the anti-inflammatory factor IL-10. Administration of Her treatment increased the content of the anti-inflammatory factor IL-10 in lung tissues, promote apoptosis and clearance of Fth1hi Neu, reduce the aggregation of Fth1hi Neu in lung tissues, and ameliorate the inflammatory injury of lung tissues. In conclusion, Her had a significant protective effect on LPS-induced inflammatory lung injury in mice, and its mechanism of action was related to elevating IL-10 levels and reducing Fth1hi Neu accumulation.

本研究旨在系统探讨Herbacetin（Her）对脂多糖（LPS）诱导的炎症性肺损伤的保护作用及其相关机制。首先，通过气管滴注LPS成功构建了小鼠炎症性肺损伤模型，并通过观察整体肺组织形态变化、肺组织病理学损伤、肺湿干重比、肺器官系数、总蛋白含量以及炎症因子含量等指标，评估了Her治疗对炎症性肺损伤小鼠的保护效果。结果显示，Her治疗能够改善LPS诱导的肺组织病理学损伤，减轻肺组织水肿，降低促炎因子TNF-α、IL-6和IL-1β的含量，并减少炎症细胞数量。同时，我们的研究结果还显示，在LPS诱导的炎症性肺损伤小鼠的肺组织中存在两种不同位置的嗜中性粒细胞亚群（Fth1hi Neu和Prok2hi Neu），LPS刺激促进了Fth1hi Neu的聚集和在肺组织中的促炎因子释放，伴随着抗炎因子IL-10含量的降低。Her治疗能够增加肺组织中抗炎因子IL-10的含量，促进Fth1hi Neu的凋亡和清除，减少肺组织中Fth1hi Neu的聚集，并改善肺组织的炎症损伤。总之，Her对小鼠LPS诱导的炎症性肺损伤具有显著的防护作用，其作用机制与提高IL-10水平和降低Fth1hi Neu积累相关。