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Selective suppression of M1 macrophages is involved in zinc inhibition of liver fibrosis in mice
The Journal of Nutritional Biochemistry ( IF 5.6 ) Pub Date : 2021-06-10 , DOI: 10.1016/j.jnutbio.2021.108802
Chengxia Xie 1 , Lin Wan 1 , Chen Li 1 , Yinrui Feng 1 , Y James Kang 2
Affiliation  

Zinc deficiency is common in the liver of patients with chronic liver disease. Zinc supplementation suppresses the progression of liver fibrosis induced by bile duct ligation (BDL) in mice. The present study was undertaken to specifically investigate a possible mechanism by which zinc plays this role in the liver. Kunming mice were subjected to BDL for 4 weeks to induce liver fibrosis, and concomitantly treated with zinc sulfite or saline as control by gavage once a day. The results showed that zinc supplementation significantly suppressed liver fibrosis and inflammation along with inhibition of hepatic stellate cells activation induced by BDL. These inhibitory effects were accompanied by the reduction of collagen deposition and a significant reduction of macrophage infiltration affected livers. Importantly, zinc selectively inhibited M1 macrophage polarization and M1-related inflammatory cytokines. This inhibitory effect was further confirmed by the reduction of relevant biomarkers of M1 macrophages including inducible NO synthase (iNOS), monocyte chemotactic protein-1 (MCP-1/CCL2), and tumor necrosis factor-α in the zinc supplemented BDL livers. In addition, zinc inhibition of M1 macrophages was associated with a decrease of Notch1 expression. Taken together, these data indicated that zinc supplementation inhibited liver inflammation and fibrosis in BDL mice through selective suppression of M1 macrophages, which is associated with inhibition of Notch1 pathway in M1 macrophage polarization.



中文翻译:

选择性抑制 M1 巨噬细胞参与锌抑制小鼠肝纤维化

慢性肝病患者的肝脏缺锌很常见。补充锌可以抑制小鼠胆管结扎(BDL)引起的肝纤维化的进展。本研究的目的是专门研究锌在肝脏中发挥这一作用的可能机制。昆明小鼠接受BDL 4周诱导肝纤维化,同时用亚硫酸锌或生理盐水作为对照,每天灌胃一次。结果表明,补充锌可显着抑制肝纤维化和炎症,同时抑制 BDL 诱导的肝星状细胞活化。这些抑制作用伴随着胶原沉积的减少和受影响肝脏的巨噬细胞浸润的显着减少。重要的是,锌选择性抑制 M1 巨噬细胞极化和 M1 相关炎症细胞因子。在补充锌的 BDL 肝脏中,M1 巨噬细胞相关生物标志物的减少进一步证实了这种抑制作用,包括诱导型 NO 合酶 (iNOS)、单核细胞趋化蛋白-1 (MCP-1/CCL2) 和肿瘤坏死因子-α。此外,锌对 M1 巨噬细胞的抑制与 Notch1 表达的减少有关。综上所述,这些数据表明,补锌通过选择性抑制 M1 巨噬细胞抑制 BDL 小鼠的肝脏炎症和纤维化,这与抑制 M1 巨噬细胞极化中的 Notch1 通路有关。

更新日期:2021-07-04
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