肠道微生态通过TLR4/MAPK/CXCR2信号通路调节中性粒细胞募集，促进肝脏缺血/再灌注损伤
Intestinal microecology regulates neutrophil recruitment through TLR4/MAPK/CXCR2 signaling pathway to promote liver ischemia/reperfusion injury.
摘要(中文译文)
肝脏缺血/再灌注损伤（IRI）是失血性休克、肝切除术和肝移植的主要并发症。肠道微生态在多种人类疾病中发挥重要作用。本研究旨在阐明肠道微生态在肝脏IRI中的作用及其潜在机制。构建肝脏IRI小鼠模型，并通过苏木精-伊红染色、酶联免疫吸附试验和萘酚AS-D氯乙酸酯酶染色进行验证。采用流式细胞术和蛋白质印迹分析评估肠道微生态在肝脏IRI中的功能。此外，通过一系列分子实验评估肠道微生态在肝脏IRI中的作用机制。结果显示，与肠道微生态失调相关的肝脏IRI表现为肝中性粒细胞浸润增加、MAPK通路激活及炎性细胞因子产生增多。对假手术组、IRI组、IRI+抗生素预处理组和粪菌移植（FT）组粪便样本进行16S rRNA基因测序，揭示了微生物群落改变，其中拟杆菌门和厚壁菌门丰度的变化与肝损伤及中性粒细胞募集相关。PCA、PCoA和分类学谱分析进一步证实了肠道微生物群落的组别依赖性重塑。使用IRI供体小鼠粪便微生物进行FT可加重肝脏中性粒细胞浸润、MAPK/CXCR2激活和炎症反应，而TAK-242介导的TLR4阻断可减弱这些效应。总体而言，本研究提示肠道菌群失调可能通过促进中性粒细胞募集加重肝脏IRI，至少部分通过TLR4/MAPK/CXCR2轴实现，揭示了可能作为治疗靶点的新型微生物-免疫-肝脏相互作用。
Abstract
Liver ischemia/reperfusion injury (IRI) is a major complication of hemorrhagic shock, hepatectomy and liver transplantation. Intestinal microecology has momentous functions in various human diseases. The present study aimed to elucidate the role and underlying mechanism of intestinal microecology in liver IRI. A liver IRI mouse model was constructed and validated using hematoxylin and eosin staining, enzyme-linked immunosorbent assay and Naphthol AS-D chloroacetate esterase staining. The function of intestinal microecology in liver IRI was evaluated using flow cytometry and western blot analysis. Moreover, the mechanisms of intestinal microecology in liver IRI were assessed using a series of molecular experiments. The results revealed that liver IRI associated with intestinal microecology dysbiosis exhibited increased hepatic neutrophil infiltration, MAPK pathway activation and inflammatory cytokine production. The 16 S rRNA gene sequencing of fecal samples from Sham, IRI, IRI+antibiotic pre-treatment and fecal transplantation (FT) groups revealed microbial community alterations, with shifts in Bacteroidota and Firmicutes abundance associated with liver injury and neutrophil recruitment. PCA, PCoA and taxonomic profiling further confirmed group-dependent remodeling of the gut microbial community. FT using fecal microbiota from IRI donor mice exacerbated liver neutrophil infiltration, MAPK/CXCR2 activation and inflammatory responses, whereas TAK-242-mediated TLR4 blockade attenuated these effects. Overall, the present study suggests that gut microbiota dysbiosis may enhance liver IRI by promoting neutrophil recruitment, at least in part through the TLR4/MAPK/CXCR2 axis, revealing a novel microbe-immune-liver interaction that may be targeted therapeutically.
如何引用
AMA
Xiaobing Yang, Junbin Zhang, Ningxiang Jiang, Libin Yang, Hongwei Li, Yu Dong, et al. Intestinal microecology regulates neutrophil recruitment through TLR4/MAPK/CXCR2 signaling pathway to promote liver ischemia/reperfusion injury.. Journal of bioenergetics and biomembranes. 2026; doi:10.1007/s10863-026-10115-z.
APA
Xiaobing Yang, Junbin Zhang, Ningxiang Jiang, Libin Yang, Hongwei Li, Yu Dong, et al (2026). Intestinal microecology regulates neutrophil recruitment through TLR4/MAPK/CXCR2 signaling pathway to promote liver ischemia/reperfusion injury.. Journal of bioenergetics and biomembranes. https://doi.org/10.1007/s10863-026-10115-z
GB/T 7714
Xiaobing Yang, Junbin Zhang, Ningxiang Jiang, Libin Yang, Hongwei Li, Yu Dong, et al. Intestinal microecology regulates neutrophil recruitment through TLR4/MAPK/CXCR2 signaling pathway to promote liver ischemia/reperfusion injury.[J]. Journal of bioenergetics and biomembranes, 2026 doi:10.1007/s10863-026-10115-z.
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