Mechanistic study on the ameliorative effects of butyrate on hepatic ischemia⁃reperfusion injury

ZHAO Hanxiang; LI Mingwei; LUO Ming; NA Shufang; YE Qifa

doi:10.14188/j.1671-8852.2026.0914

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Mechanistic study on the ameliorative effects of butyrate on hepatic ischemia⁃reperfusion injury

更新时间：2026-10-26

- Mechanistic study on the ameliorative effects of butyrate on hepatic ischemia⁃reperfusion injury
- Medical Journal of Wuhan University Pages: 1-10(2026)
- 作者机构：
  
  武汉大学中南医院/武汉大学肝胆疾病研究院/武汉大学移植医学中心/移植医学技术湖北省重点实验室湖北武汉 430071
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2026.0914
  CLC： R575
- Received：02 June 2026，
  
  Online First：26 October 2026，
- 稿件说明：
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ZHAO Hanxiang, LI Mingwei, LUO Ming, et al. Mechanistic study on the ameliorative effects of butyrate on hepatic ischemia⁃reperfusion injury[J/OL]. Medical Journal of Wuhan University, 2026, 1-10.
DOI：

ZHAO Hanxiang, LI Mingwei, LUO Ming, et al. Mechanistic study on the ameliorative effects of butyrate on hepatic ischemia⁃reperfusion injury[J/OL]. Medical Journal of Wuhan University, 2026, 1-10. DOI： 10.14188/j.1671-8852.2026.0914.

摘要

目的

探讨肠道丁酸代谢对肝脏缺血再灌注损伤（IRI）的作用及其分子机制。

方法

通过70%肝脏缺血建立小鼠IRI模型，利用链霉素建立的产丁酸菌缺失模型，外源性给予丁酸盐补充干预，检测不同模型下血清转氨酶、病理、凋亡、炎症及线粒体超微结构，结合转录组测序、Western Blot等验证组蛋白去乙酰化酶3(HDAC3)/NF⁃κB通路的变化。

结果

链霉素处理加重了小鼠IRI，转氨酶ALT和AST水平显著升高，肝脏呈现更为广泛的融合性坏死、肝索断裂及剧烈的炎症细胞浸润，细胞凋亡增多，线粒体嵴的崩解与空泡化加重。外源性补充丁酸盐显著逆转了上述病理表型。机制上，丁酸盐抑制HDAC3活性，稳定IκBα，阻断NF⁃κB p65核转位及下游炎症因子释放。

结论

肠道产丁酸菌的缺失会增加IRI易感性。丁酸盐通过抑制HDAC3/NF⁃κB通路发挥抗炎和保护线粒体作用，围手术期恢复肠道产丁酸菌生态位或补充丁酸盐有望成为减轻肝脏IRI的新策略。

Abstract

Objective

To explore the role of intestinal butyrate metabolism in liver ischemia⁃reperfusion injury (IRI) and its molecular mechanism.

Methods

A mouse model of IRI was established by 70% liver ischemia. A butyrate⁃producing bacteria⁃deficient model was established by streptomycin treatment. Exogenous butyrate supplementation was used for intervention. Serum enzymes

pathology

apoptosis

inflammation and mitochondrial ultrastructure were detected in different models. The changes of histone deacetylase 3 （HDAC3)/NF⁃κB pathway were verified by transcriptome sequencing and Western Blot.

Results

Streptomycin treatment aggravated IRI in mice

with significantly increased ALT and AST levels

more extensive confluent necrosis

disrupted hepatic cords and severe inflammatory cell infiltration in the liver

increased apoptosis

and aggravated mitochondrial cristae disintegration and vacuolization. Exogenous butyrate supplementation significantly reversed the above pathological phenotypes. Mechanistically

butyrate inhibited HDAC3 activity

stabilized IκBα

blocked NF⁃κB p65 nuclear translocation and the release of downstream inflammatory factors.

Conclusion

The absence of intestinal butyrate⁃producing bacteria increases the susceptibility to IRI. Butyrate exerts anti⁃inflammatory and mitochondrial protective effects by inhibiting the HDAC3/NF⁃κB pathway. Restoring the intestinal butyrate⁃producing bacteria niche or supplementing butyrate during the perioperative period may become a new strategy to alleviate liver IRI.

关键词

Keywords

references

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