Cai Quan, Jin Yan, Jia Ziyi, Liu Zhi
Department of Emergency, The First Hospital of China Medical University, Shenyang, China.
Front Pharmacol. 2022 Apr 1;13:856441. doi: 10.3389/fphar.2022.856441. eCollection 2022.
To explore the molecular mechanism of lung injury caused by paraquat (PQ) poisoning by investigating miR-199-mediated SET. A paraquat poisoning model was established in C57BL/6 male mice via intraperitoneal injection of paraquat. The mice were transfected with miR-199 siRNA and or mimic. After 14 days of treatment, pathophysiological changes of the lung were observed and lung tissue was analyzed via Hematoxylin-Eosin staining. The levels of miR-199, SETs, surfactant protein SP-A and SP-B, and inflammatory and oxidative factors were analyzed by qPCR, Western Blot, and ELISA kits. A acute lung-injury (ALI) model was established using PQ treatment and confirmed with edema of pulmonary endothelium with low electronic density of endothelial cytoplasm, presence of protein-rich fluid, and numerous erythrocytes in alveolar space, concentric figures of damaged tubular myelin, alveolar destruction, and increase in inflammatory cell numbers. Compared with the control group, miR-199 and SET levels were reduced in the PQ-treated group. miR-199 siRNA increased the SET level, inflammatory and oxidative levels, and reduced the levels of SP-A and SP-B, and miR-199 mimic reduced the SET level, inflammatory and oxidative levels, and increased the levels of SP-A and SP-B. PQ treatment reduced miR-199 level. Paraquat induces ALI by affecting miR-199-mediated SET.
通过研究miR-199介导的SET来探讨百草枯（PQ）中毒所致肺损伤的分子机制。通过腹腔注射百草枯在C57BL/6雄性小鼠中建立百草枯中毒模型。将小鼠用miR-199 siRNA和/或模拟物转染。治疗14天后，观察肺的病理生理变化，并通过苏木精-伊红染色分析肺组织。通过qPCR、蛋白质免疫印迹法和酶联免疫吸附测定试剂盒分析miR-199、SET、表面活性蛋白SP-A和SP-B以及炎症和氧化因子的水平。使用PQ处理建立急性肺损伤（ALI）模型，并通过肺内皮水肿、内皮细胞质电子密度低、肺泡腔内存在富含蛋白质的液体和大量红细胞、受损管状髓磷脂的同心圆结构、肺泡破坏以及炎症细胞数量增加来证实。与对照组相比，PQ处理组中miR-199和SET水平降低。miR-199 siRNA增加SET水平、炎症和氧化水平，并降低SP-A和SP-B水平，而miR-199模拟物降低SET水平、炎症和氧化水平，并增加SP-A和SP-B水平。PQ处理降低了miR-199水平。百草枯通过影响miR-199介导的SET诱导ALI。
