Maresin1 alleviates liver ischemia/reperfusion injury by reducing liver macrophage pyroptosis

作者全名："Li, Tong; Zeng, Houshuai; Xian, Wenjing; Cai, Hongxing; Zhang, Jianbo; Zhou, Shiji; Yang, Yingxue; Luo, Min; Zhu, Peng"

作者地址："[Li, Tong; Zeng, Houshuai; Cai, Hongxing; Zhang, Jianbo; Zhou, Shiji; Zhu, Peng] Chongqing Med Univ, Affiliated Hosp 2, Dept Gastrointestinal Surg, 74 Linjiang Rd, Chongqing 400010, Peoples R China; [Xian, Wenjing] Chongqing Med Univ, Affiliated Hosp 1, Dept Anesthesiol, Chongqing, Peoples R China; [Yang, Yingxue] Chongqing Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Chongqing, Peoples R China; [Luo, Min] Chongqing Med Univ, Affiliated Hosp 2, Dept Infect Dis, Chongqing, Peoples R China"

通信作者："Zhu, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Gastrointestinal Surg, 74 Linjiang Rd, Chongqing 400010, Peoples R China."

来源：JOURNAL OF TRANSLATIONAL MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001026241000001

JCR分区：Q1

影响因子：6.1

年份：2023

卷号：21

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Maresin1; Ischemia; reperfusion; Liver; Mitochondria; Pyroptosis

摘要："BackgroundCell pyroptosis has a strong proinflammatory effect, but it is unclear whether pyroptosis of liver macrophages exacerbates liver tissue damage during liver ischemia-reperfusion (I/R) injury. Maresin1 (MaR1) has a strong anti-inflammatory effect, and whether it can suppress liver macrophage pyroptosis needs further study.MethodsThis study aimed to investigate whether MaR1 can alleviate liver I/R injury by inhibiting macrophage pyroptosis. The effects of MaR1 on cell pyroptosis and mitochondrial damage were studied by dividing cells into control, hypoxia/reoxygenation, and hypoxia/reoxygenation + MaR1 groups. Knocking out RORa was used to study the mechanism by which MaR1 exert its protective effects. Transcriptome analysis, qRT-PCR and Western blotting were used to analyze gene expression. Untargeted metabolomics techniques were used to analyze metabolite profiles in mice. Flow cytometry was used to assess cell death and mitochondrial damage.ResultsWe first found that MaR1 significantly reduced liver I/R injury. We observed that MaR1 decreased liver I/R injury by inhibiting liver macrophage pyroptosis. Then, we discovered that MaR1 promotes mitochondrial oxidative phosphorylation, increases the synthesis of ATP, reduces the generation of ROS, decreases the impairment of mitochondrial membrane potential and inhibits the opening of mitochondrial membrane permeability transition pores. MaR1 inhibits liver macrophage pyroptosis by protecting mitochondria. Finally, we found that MaR1 exerts mitochondrial protective effects through activation of its nuclear receptor RORa and the PI3K/AKT signaling pathway.ConclusionsDuring liver I/R injury, MaR1 can reduce liver macrophage pyroptosis by reducing mitochondrial damage, thereby reducing liver damage."

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