Wan Hui, Zhang Yuxin, Gao Zhicheng, Shan Guanyue, Yin Jianing, Li Haijun
Department of Transplantation Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin Province, 130061, China.
Department of Transplantation Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin Province, 130061, China; Department of Bioengineering, Pharmacy School of Jilin University, Changchun, Jilin Province, 130021, China.
Eur J Pharmacol. 2025 Nov 5;1006:178149. doi: 10.1016/j.ejphar.2025.178149. Epub 2025 Sep 18.
Acute lung injury (ALI) has attracted considerable attention because of its high mortality rate. Procyanidin B2 (PCB2) is widely present in various dietary foods and plants. However, the effects of PCB2 on lung macrophages in LPS-induced ALI and the underlying molecular mechanisms have not yet been reported. The objective of the present study was to examine the effects of PCB2 on LPS-induced ALI and macrophages and the related mechanisms. Immunofluorescence, ELISA, qRT‒PCR, H&E staining and Western blotting were used for in vivo and in vitro experiments. The outcomes showed that PCB2 effectively alleviated ALI by reducing the lung wet‒dry (W/D) ratio, improving histopathological changes, decreasing the levels of IL-1β, TNF-α, IL-6 and reducing M1 polarization of lung macrophages. Both in vitro and in vivo, PCB2 inhibited the activation of the NF-κB and JAK2/STAT1 signaling pathways, suppressed the expression of Caspase-1, NLRP3, ASC proteins, and the expression of CD80, CD86, and iNOS, while increasing the expression of CD206. Our findings suggested that PCB2 inhibited the activation of the NF-κB and JAK2/STAT1 signaling pathways, thereby alleviating macrophage pyroptosis and M1 polarization in LPS-caused ALI. PCB2 holds considerable promise as a potential therapeutic option for ALI.
急性肺损伤（ALI）因其高死亡率而备受关注。原花青素B2（PCB2）广泛存在于各种膳食食品和植物中。然而，PCB2对脂多糖（LPS）诱导的ALI中肺巨噬细胞的影响及其潜在分子机制尚未见报道。本研究的目的是探讨PCB2对LPS诱导的ALI和巨噬细胞的影响及其相关机制。采用免疫荧光、酶联免疫吸附测定（ELISA）、实时定量逆转录聚合酶链反应（qRT‒PCR）、苏木精-伊红（H&E）染色和蛋白质印迹法进行体内和体外实验。结果表明，PCB2通过降低肺组织干湿比（W/D）、改善组织病理学变化、降低白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、IL-6水平以及减少肺巨噬细胞的M1极化，有效减轻了ALI。在体外和体内，PCB2均抑制核因子κB（NF-κB）和Janus激酶2/信号转导和转录激活因子1（JAK2/STAT1）信号通路的激活，抑制半胱天冬酶-1（Caspase-1）、NOD样受体蛋白3（NLRP3）、凋亡相关斑点样蛋白（ASC）的表达以及CD80、CD86和诱导型一氧化氮合酶（iNOS）的表达，同时增加CD206的表达。我们的研究结果表明，PCB2抑制NF-κB和JAK2/STAT1信号通路的激活，从而减轻LPS诱导的ALI中的巨噬细胞焦亡和M1极化。PCB2作为ALI的一种潜在治疗选择具有很大的前景。
