Department of Emergency, the First People's Hospital of Yunnan Province,the Affiliated Hospital of Kunming University of Science and Technology, Xishan District, No.157 Jinbi Road Yunnan Province, Kunming City, China.
Department of Basic Research Institute, the First People's Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology,Xishan District, No.157 Jinbi Road Yunnan Province, Kunming City, China.
Inflammation. 2022 Dec;45(6):2256-2267. doi: 10.1007/s10753-022-01688-z. Epub 2022 Jun 8.
WIN 55212-2 is an endocannabinoids analogue that has been reported to have anti-inflammatory and anti-fibrosis effects on different models. In this study, we investigated the protective effects of WIN 55212-2 on paraquat (PQ)-induced poison on mice especially on lung injury. Mice were administrated with different dose of PQ and thereafter treated with 0.2 mg/kg or 1 mg/kg WIN 55212-2. The survival of mice was recorded during 4 weeks of observation. Twenty-eight days after PQ treatment, the cell population and inflammatory factors IL-6, IL-10, and TNF-α were measured in bronchoalveolar lavage fluid (BALF). Pulmonary fibrosis was evaluated by Masson staining. Our results showed that WIN 55212-2 treatment reduced PQ-induced mortality of mice in a dose dependent manner. It decreased the number of inflammation-associated cells, as well as the level of pro-inflammatory factors in BALF (P < 0.05). WIN 55212-2 increased M2 cells in BALF (P < 0.05), improved the lung histology, reduced fibrosis formation, and decreased TGF-β, α-SMA and PDGFRa expression. The protective effects of WIN 55212-2 on PQ-induced lung injury and fibrosis were associated with an increase inM2 cells and increased expressions of IL-10, CD163, and CD206, suggesting that polarization of M2 macrophages may be involved in WIN 55212-2 protective effects on PQ-induced lung injury.
WIN 55212-2 是一种内源性大麻素类似物，已被报道在不同模型中具有抗炎和抗纤维化作用。在这项研究中，我们研究了 WIN 55212-2 对百草枯（PQ）诱导的中毒对小鼠，特别是对肺损伤的保护作用。小鼠给予不同剂量的 PQ，然后用 0.2mg/kg 或 1mg/kg 的 WIN 55212-2 治疗。在观察的 4 周内记录小鼠的存活率。PQ 处理 28 天后，测量支气管肺泡灌洗液（BALF）中的细胞群和炎症因子 IL-6、IL-10 和 TNF-α。通过 Masson 染色评估肺纤维化。我们的结果表明，WIN 55212-2 治疗以剂量依赖的方式降低 PQ 诱导的小鼠死亡率。它减少了与炎症相关的细胞数量，以及 BALF 中促炎因子的水平（P<0.05）。WIN 55212-2 增加了 BALF 中的 M2 细胞（P<0.05），改善了肺组织学，减少了纤维化形成，并降低了 TGF-β、α-SMA 和 PDGFRa 的表达。WIN 55212-2 对 PQ 诱导的肺损伤和纤维化的保护作用与 M2 细胞的增加以及 IL-10、CD163 和 CD206 的表达增加有关，表明 M2 巨噬细胞的极化可能参与了 WIN 55212-2 对 PQ 诱导的肺损伤的保护作用。
