线粒体分裂抑制剂Mdivi-1对脓毒症大鼠肠道屏障功能的保护作用

汤春琼; 朱娱; 王易; 叶蕤; 刘良明; 李涛; 毛庆祥

doi:10.16016/j.2097-0927.202303166

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线粒体分裂抑制剂Mdivi-1对脓毒症大鼠肠道屏障功能的保护作用

基础医学 | 更新时间：2026-01-09

- 线粒体分裂抑制剂Mdivi-1对脓毒症大鼠肠道屏障功能的保护作用
- Mitochondrial division inhibitor Mdivi-1 protects intestinal barrier function in septic rats
- 陆军军医大学学报 2024年46卷第5期页码：419-426
- 作者机构：
  
  1.400042 重庆，陆军特色医学中心麻醉科
  2.400042 重庆，陆军特色医学中心野战外科研究部战伤休克与输血研究室，创伤与化学中毒全国重点实验室
- 作者简介：
  
  [毛庆祥，E-mail：maomaosmmu@126.com MAO Qingxiang, E-mail: maomaosmmu@126.com
- 基金信息：
  
  国家自然科学基金面上项目(82270523)
- DOI：10.16016/j.2097-0927.202303166
  中图分类号： R322.45;R631.1;R977.6
- 收稿：2023-03-28，
  
  修回：2023-06-12，
  
  纸质出版：2024-03-15
- 稿件说明：
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汤春琼, 朱娱, 王易, 等. 线粒体分裂抑制剂Mdivi-1对脓毒症大鼠肠道屏障功能的保护作用[J]. 陆军军医大学学报, 2024,46(5):419-426.

Chunqiong TANG, Yu ZHU, Yi WANG, et al. Mitochondrial division inhibitor Mdivi-1 protects intestinal barrier function in septic rats[J]. Journal of Army Medical University, 2024, 46(5): 419-426.
汤春琼, 朱娱, 王易, 等. 线粒体分裂抑制剂Mdivi-1对脓毒症大鼠肠道屏障功能的保护作用[J]. 陆军军医大学学报, 2024,46(5):419-426. DOI： 10.16016/j.2097-0927.202303166.

Chunqiong TANG, Yu ZHU, Yi WANG, et al. Mitochondrial division inhibitor Mdivi-1 protects intestinal barrier function in septic rats[J]. Journal of Army Medical University, 2024, 46(5): 419-426. DOI： 10.16016/j.2097-0927.202303166.

摘要

目的

拟探讨线粒体分裂抑制剂Mdivi-1对脓毒症大鼠肠道屏障功能的保护作用。

方法

采用盲肠结扎穿孔术(cecal ligation and puncture，CLP)复制大鼠脓毒症模型，根据脓毒症救治指南采用乳酸林格氏液(35 mL/kg)进行常规复苏，输液速度3 mL/h。同时在常规复苏的基础上静脉予以1 mg/kg Mdivi-1进行治疗。复苏结束后2 h观察各组大鼠肠道屏障功能、肠道中闭锁小带蛋白(zonula occludes-1，ZO-1)的表达、小肠病理变化、血清炎症因子肿瘤坏死因子α(tumor necrosis factor α，TNF-α)和白介素1-β(Interleukin-1β，IL-1β)的浓度、平均动脉血压(mean arterial blood pressure，MAP)和生存时间及72 h存活率。

结果

与假手术组相比，脓毒症大鼠肠通透性明显增加，D-乳酸明显升高，血清中炎性因子TNF-α和IL-1β浓度显著增高(

＜0.05)；病理结果显示肠绒毛断裂，腺体萎缩，炎性细胞显著增多。常规复苏治疗后，与脓毒症组相比，血清中TNF-α和IL-1β浓度、肠通透性、D-乳酸浓度轻微降低，肠绒毛紊乱轻微改善，提示常规复苏治疗后对脓毒症的保护作用是有限的。与常规治疗组相比，常规治疗联合线粒体分裂抑制剂Mdivi-1治疗后大鼠血清中TNF-α和IL-1β浓度、肠通透性、D-乳酸浓度显著降低(

＜0.05)，病理结果显示肠绒毛结构清晰，炎性细胞浸润明显改善。肠组织免疫荧光结果显示，与假手术组相比，脓毒症后紧密连接发生断裂，Mdivi-1治疗后较脓毒症组紧密连接断裂发生明显好转。细胞水平上，LPS刺激后肠上皮细胞间ZO-1表达量显著降低(

＜0.05)，Mdivi-1治疗后可逆转LPS导致的ZO-1表达量的降低(

＜0.05)。

结论

Mdivi-1对脓毒症大鼠的肠道屏障功能具有保护作用，其机制可能是通过调节ZO-1的表达。

Abstract

Objective

To investigates the protective effect of mitochondrial division inhibitor

Mdivi-1

on intestinal barrier function in septic rats.

Methods

A total of 160 SD rats were randomly and equally divided into sham operation group

sepsis group (established by cecal ligation and puncture)

conventional treatment group

and Mdivi-1 treatment group. The rats from the conventional treatment group were given lactated Ringer's solution (35 mL/kg) at an infusion rate of 3 mL/h according to the guidelines for sepsis treatment

and those from the Mdivi-1 treatment group were added with intravenous administration of 1 mg/kg Mdivi-1 for resuscitation on the basis of conventional treatment. After 2 h of resuscitation

intestinal barrier function

intestinal expression of zonula occludes-1 (ZO-1)

pathological changes in small intestine

serum concentrations of inflammatory cytokines (including TNF-α and IL-1β)

mean arterial blood pressure (MAP)

survival time and 72-hour survival rate were observed. Intestinal epithelial cells (IECs) were employed to observe the effect of Mdivi-1 on the expression of ZO-1 under the simulation of LPS.

Results

The septic rats had significantly increased intestinal permeability

D-lactate level and serum concentrations of TNF-α and IL-1β when compared with those of the sham operation group (

0.05)

and showed intestinal villus rupture

glandular atrophy

and great amount of inflammatory cells in pathological observation. Conventional treatment resulted in slightly decreased serum concentrations of TNF-α and IL-1β

intestinal permeability

and D-lactate level (

0.05)

and mildly improved intestinal villus disturbance when compared with the sepsis group. Mdivi-1 treatment combined with conventional treatment significantly decreased serum concentrations of TNF-α and IL-1β

intestinal permeability

and D-lactate level in comparison with septic rats (

0.05)

and pathological results showed clear intestinal villus structure and significantly improved inflammatory cell infiltration. The immunohistochemical results of intestinal tissue showed that ruptured tight junction was observed after sepsis

and Mdivi-1 treatment significantly improved the tight junction rupture. At the cellular level

the expression level of ZO-1 between IECs was significantly decreased after LPS stimulation (

0.05)

and Mdivi-1 treatment increased LPS-induced decrease in ZO-1 expression (

0.05).

Conclusion

Conclusion Mdivi-1 has a protective effect on intestinal barrier function in septic rats

which may be through its regulating ZO-1 expression.

关键词

Keywords

references

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