Protective effect of remimazolam on intestinal barrier function in septic mice

WANG Weifei; DENG Haoyue; DU Yunxia; DU Zhongyuan; LIU Liangming; LI Tao; MAO Qingxiang

doi:10.16016/j.2097-0927.202504115

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Protective effect of remimazolam on intestinal barrier function in septic mice

Military Medicine | 更新时间：2025-07-27

- Protective effect of remimazolam on intestinal barrier function in septic mice
- Journal of Army Medical University Vol. 47, Issue 15, Pages: 1806-1814(2025)
- 作者机构：
  
  1.陆军特色医学中心（第三军医大学大坪医院）：，麻醉科，重庆
  2.陆军特色医学中心（第三军医大学大坪医院）：，野战外科研究部战伤休克与输血研究室，重庆
- 作者简介：
  
  MAO Qingxiang， E-mail： qxmao@tmmu.edu.cn
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(82302437)
- DOI：10.16016/j.2097-0927.202504115
  CLC： R574;R631.2;R971.2
- Received：28 April 2025，
  
  Revised：04 July 2025，
  
  Accepted：05 July 2025，
  
  Published：15 August 2025
- 稿件说明：
移动端阅览
王维飞，邓皓月，杜云霞，等.瑞马唑仑对脓毒症小鼠肠道屏障功能的保护作用［J］.陆军军医大学学报，2025，47（15）：1806-1814.DOI：10.16016/j.2097-0927.202504115.

‍WANG W F，DENG H Y，DU Y X，et al.Protective effect of remimazolam on intestinal barrier function in septic mice［J］.J Army Med Univ，2025，47（15）：1806-1814.DOI：10.16016/j.2097-0927.202504115.
王维飞，邓皓月，杜云霞，等.瑞马唑仑对脓毒症小鼠肠道屏障功能的保护作用［J］.陆军军医大学学报，2025，47（15）：1806-1814.DOI：10.16016/j.2097-0927.202504115. DOI：

‍WANG W F，DENG H Y，DU Y X，et al.Protective effect of remimazolam on intestinal barrier function in septic mice［J］.J Army Med Univ，2025，47（15）：1806-1814.DOI：10.16016/j.2097-0927.202504115. DOI：

摘要

目的

探讨新型苯二氮䓬类镇静药瑞马唑仑（remimazolam，Remi）对脓毒症小鼠肠道屏障功能的保护作用。

方法

采用盲肠结扎穿孔（cecal ligation and puncture，CLP）构建脓毒症模型，将96只成年雄性SPF级C57BL/6小鼠按随机数字表法分为假手术（Sham）组、脓毒症（Sepsis）组、脓毒症+瑞马唑仑（Sepsis+Remi）组，记录各组小鼠72 h存活情况和存活时间，观察小鼠肠道病理结构、肠道屏障功能指标、肠道ZO-1蛋白表达及肠道巨噬细胞极化变化来评估Remi对肠道屏障功能的影响。采取脂多糖（lipopolysaccharide，LPS）刺激RAW264.7细胞24 h构建脓毒症体外模型，分为对照（Control）组、LPS组、瑞马唑仑干预（LPS+Remi）组，免疫荧光染色观察巨噬细胞表型、线粒体形态及线粒体活性氧（mitochondrial reactive oxygen species，MtROS），Western blot检测诱导型一氧化碳合酶（inducible nitric oxide synthase， iNOS）和甘露糖受体（cluster of differentiation 206，CD206）蛋白表达。

结果

与Sepsis组相比，Remi干预后脓毒症小鼠的存活率从12.50%提升至68.75%，存活时间显著延长（

0.05），肠道绒毛结构部分恢复，间质水肿程度减轻，炎症细胞浸润减少，功能性指标显著改善。同时，体内外实验均发现，相较于Sham组和Control组，Sepsis组和LPS组巨噬细胞iNOS表达增加、CD206表达减少（

0.05），而Sepsis+Remi组和LPS+Remi组可部分逆转此现象（

0.05）。LPS组巨噬细胞线粒体呈明显碎片化，且相较于Control组，MtROS显著增加（

0.05）；而相较于LPS组，LPS+Remi组巨噬细胞线粒体碎片化显著改善，MtROS也明显减少（

0.05）。

结论

Remi可通过调控线粒体动力失衡诱导的氧化损伤，改善巨噬细胞炎性活化，进而在保护脓毒症小鼠肠道屏障功能中发挥作用。

Abstract

Objective‍　‍To investigate the protective effects of remimazolam (Remi)

a novel benzodiazepine sedative

on intestinal barrier function in septic mice. Methods A mouse model of sepsis was established using cecal ligation and puncture (CLP). A total of 96 SPF-grade adult male C57BL/6 mice were randomized into sham operation (Sham)

sepsis (Sepsis)

and sepsis with Remi intervention (Sepsis+Remi) groups. Survival rate and survival time were recorded within 72 h after modeling. Intestinal pathological alterations

barrier functional indicators

ZO-1 expression

and macrophage polarization status were observed and detected to evaluate the effects of Remi. Lipopolysaccharide (LPS) was used to treat RAW264.7 cells for 24 h to simulate

in vitro

sepsis model. The cells were divided into control (Control)

LPS

and LPS+Remi groups. Immunofluorescence staining was performed to assess macrophage phenotype

mitochondrial morphology

and mitochondrial reactive oxygen species (MtROS)

and Western blotting was applied to detect the protein expression of iNOS and CD206. Results Compared with the sepsis group

Remi intervention s

ignificantly improved the survival rate of septic mice from 12.50% to 68.75% and markedly prolonged survival duration (

0.05). Histopathological analysis demonstrated partial restoration of intestinal villus architecture

accompanied with attenuated interstitial edema and reduced inflammatory cell infiltration after Remi intervention. Furthermore

the intervention group demonstrated significant improvement in functional indicators. Both

in vivo

and

in vitro

experiments demonstrated elevated iNOS and decreased CD206 expression in the septic mice and LPS-stimulated macrophages（

0.05）

which were partially reversed after Remi intervention. Furthermore

LPS-stimulated macrophages exhibited fragmented mitochondria and elevated MtROS level

whereas Remi intervention ameliorated these conditions（

0.05）. Conclusion‍　‍Remi protects intestinal barrier function in septic mice by mitigating mitochondrial dynamics imbalance-induced oxidative damage and ameliorating inflammatory macrophage activation.

关键词

Keywords

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