Yuan Ding, Li Yi, Hou Linlin, Yang Fang, Meng Cuicui, Yu Yanwu, Sun Changhua, Duan Guoyu, Xu Zhigao, Zhu Guiying, Guo Jianjun, Zhang Leilei, Yan Gaiqin, Chen Jihong, Yang Yanan, Zhang Yan, Gao Yanxia
Department of Emergency Medicine, Henan Key Laboratory of Emergency and Trauma Research Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Front Pharmacol. 2022 May 13;13:811372. doi: 10.3389/fphar.2022.811372. eCollection 2022.
This study explored the role of metformin (MET) in regulating the polarization of alveolar macrophages to protect against acute lung injury (ALI) in rats caused by paraquat (PQ) poisoning. The studies showed that the 35 mg/kg dose of MET increased the survival rate of rats, alleviated pathological damages to the lungs and their systemic inflammation, promoted the reduction of the pro-inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, and increased the anti-inflammatory factor IL-10 levels in the rat serum. At the same time, the MET intervention decreased the expression of M1 macrophage marker iNOS in the lungs of the PQ-poisoned rats while increasing the M2 macrophage marker, Arg1, expression. , the concentration of MET > 10 mmol/L affected NR8383 viability adversely and was concentration-dependent; however, no adverse impact on NR8383 viability was observed at MET ≤ 10 mmol/L concentration, resisting the reducing effect of PQ on NR8383 vitality. The PQ-induced NR8383 model with MET intervention showed significantly reduced secretions of IL-6 and TNF-α in NR8383, and lowered expressions of M1 macrophage markers iNOS and CD86. Additionally, MET increased IL-10 secretion and the M2 macrophage markers, Arg1 and Mrcl, expressions. Therefore, we speculate that MET could regulate alveolar macrophage polarization to protect against PQ-poisoning caused ALI.
本研究探讨了二甲双胍（MET）在调节肺泡巨噬细胞极化以保护大鼠免受百草枯（PQ）中毒所致急性肺损伤（ALI）中的作用。研究表明，35mg/kg剂量的MET可提高大鼠存活率，减轻肺部病理损伤及其全身炎症反应，促进促炎因子白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平降低，并提高大鼠血清中抗炎因子IL-10水平。同时，MET干预降低了PQ中毒大鼠肺组织中M1巨噬细胞标志物诱导型一氧化氮合酶（iNOS）的表达，同时增加了M2巨噬细胞标志物精氨酸酶1（Arg1）的表达。MET浓度>10mmol/L时对NR8383细胞活力有不良影响且呈浓度依赖性；然而，在MET浓度≤10mmol/L时未观察到对NR8383细胞活力的不良影响，抵抗了PQ对NR8383活力的降低作用。MET干预的PQ诱导NR8383模型显示NR8383中IL-6和TNF-α分泌显著减少，M1巨噬细胞标志物iNOS和CD86表达降低。此外，MET增加了IL-10分泌以及M2巨噬细胞标志物Arg1和甘露糖受体C1（Mrcl）的表达。因此，我们推测MET可调节肺泡巨噬细胞极化以保护免受PQ中毒所致的ALI。
