Zhang Peng, Yin Yuping, Wang Tao, Li Wei, Li Chengguo, Zeng Xiangyu, Yang Wenchang, Zhang Ruizhi, Tang Yu, Shi Liang, Li Ruidong, Tao Kaixiong
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Free Radic Biol Med. 2020 Feb 1;147:23-36. doi: 10.1016/j.freeradbiomed.2019.11.033. Epub 2019 Nov 27.
The liver is the most important metabolic and detoxifying organ in the human body, and liver damage can seriously affect bodily function and potentially be life threatening. Accumulating evidence suggests that maresin 1 (MaR1) exhibits protective and anti-inflammatory effects in some diseases, such as pneumonia and colitis; however, its role in acute hepatitis remains unclear. Here, we established a concanavalin A (ConA)-induced acute liver-injury mouse model to determine whether MaR1 administration can attenuate liver damage. Our results indicate that MaR1 confers protective effects against ConA-induced acute liver injury, improves liver function and survival, and reduces histopathological damage. Additionally, MaR1 attenuated the inflammatory response and reduced hepatocyte apoptosis while increasing mouse macrophage apoptosis and markedly decreasing levels of reactive oxygen species (ROS) in macrophages. We also found that MaR1 significantly inhibited ConA-induced activation of the nuclear factor-kappaB (NF-κB) pathway. This work will contribute to a better understanding of acute liver injury (ALI) and advancement towards its treatment.
肝脏是人体最重要的代谢和解毒器官,肝损伤会严重影响身体机能,甚至可能危及生命。越来越多的证据表明,maresin 1(MaR1)在某些疾病(如肺炎和结肠炎)中具有保护和抗炎作用;然而,其在急性肝炎中的作用仍不清楚。在此,我们建立了伴刀豆球蛋白A(ConA)诱导的急性肝损伤小鼠模型,以确定给予MaR1是否能减轻肝损伤。我们的结果表明,MaR1对ConA诱导的急性肝损伤具有保护作用,可改善肝功能和提高生存率,并减少组织病理学损伤。此外,MaR1减轻了炎症反应,减少了肝细胞凋亡,同时增加了小鼠巨噬细胞凋亡,并显著降低了巨噬细胞中活性氧(ROS)的水平。我们还发现,MaR1显著抑制了ConA诱导的核因子-κB(NF-κB)通路的激活。这项工作将有助于更好地理解急性肝损伤(ALI)并推动其治疗进展。