Inhibiting mitochondrial fission protects multiple organ functions in rats with concomitant explosive blast injury and hemorrhagic shock by improving microcirculation and vascular permeability

ZHU Yu; LI Qinghui; WU Yue; PENG Xiaoyong; OUYANG Xingnan; ZHANG Jie; LIU Liangming; LI Tao

doi:10.16016/j.2097-0927.202507018

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Inhibiting mitochondrial fission protects multiple organ functions in rats with concomitant explosive blast injury and hemorrhagic shock by improving microcirculation and vascular permeability

Military Medicine | 更新时间：2025-11-13

- Inhibiting mitochondrial fission protects multiple organ functions in rats with concomitant explosive blast injury and hemorrhagic shock by improving microcirculation and vascular permeability
- Journal of Army Medical University Vol. 47, Issue 21, Pages: 2581-2590(2025)
- 作者机构：
  
  陆军军医大学大坪医院战伤休克与输血研究室，创伤与化学中毒全国重点实验室，重庆
- 作者简介：
  
  LI Tao， E-mail： lt200132@tmmu.edu.cn
- 基金信息：
  
  General Program of National Natural Science Foundation of China(82172195);the Project of Science and Technology Research of Chongqing Education Commission(KJZD-K202512803)
- DOI：10.16016/j.2097-0927.202507018
  CLC： R605.971;R642;R977
- Received：04 July 2025，
  
  Revised：2025-10-20，
  
  Accepted：21 October 2025，
  
  Published：15 November 2025
- 稿件说明：
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朱娱，李清晖，吴跃，等.抑制线粒体分裂通过改善微循环及血管通透性保护爆炸失血性休克大鼠的多器官功能［J］.陆军军医大学学报，2025，47（21）：2581-2590.DOI：10.16016/j.2097-0927.202507018.

ZHU Y，LI Q H，WU Y，et al.Inhibiting mitochondrial fission protects multiple organ functions in rats with concomitant explosive blast injury and hemorrhagic shock by improving microcirculation and vascular permeability［J］.J Army Med Univ，2025，47（21）：2581-2590.DOI：10.16016/j.2097-0927.202507018.
朱娱，李清晖，吴跃，等.抑制线粒体分裂通过改善微循环及血管通透性保护爆炸失血性休克大鼠的多器官功能［J］.陆军军医大学学报，2025，47（21）：2581-2590.DOI：10.16016/j.2097-0927.202507018. DOI：

ZHU Y，LI Q H，WU Y，et al.Inhibiting mitochondrial fission protects multiple organ functions in rats with concomitant explosive blast injury and hemorrhagic shock by improving microcirculation and vascular permeability［J］.J Army Med Univ，2025，47（21）：2581-2590.DOI：10.16016/j.2097-0927.202507018. DOI：

摘要

目的

探究线粒体分裂抑制剂1（mitochondrial division inhibitor 1，Mdivi-1）对爆炸合并失血性休克大鼠器官功能的保护作用。

方法

采用随机数字表法将192只12周龄SD大鼠（雌雄各半，体质量约220 g）分为6组（

=32）：假手术（Sham）组（仅沿腹白线开口，不予其他处理），爆炸失血性休克（explosion combined with hemorrhagic shock，ESH）组（采用热辐射与冲击波致伤+股动脉失血建立ESH模型，模型成功后不进行复苏干预），乳酸林格氏液（Lactated Ringer’s solution，LR）复苏（ESH+LR）组（ESH模型成功后，经股静脉输注乳酸林格氏液进行复苏），不同剂量（LR+0.

1 mg/kg Mdivi-1组、LR+ 0.5 mg/kg Mdivi-1组、LR+1.0 mg/kg Mdivi-1组）的Mdivi-1治疗组（ESH模型成功后，在LR治疗的基础上，经股静脉分别输注0.1、0.5和1.0 mg/kg 的Mdivi-1）。采用荧光蛋白示踪法，通过检测大鼠肺脏、肾脏组织中荧光蛋白的渗漏量，评估血管通透性；通过伊文思蓝染色法检测肠道通透性和肺血管通透性；采用激光多普勒血流仪监测肝脏、肾脏、肠道组织血流灌注；检测心肌损伤标志物肌钙蛋白I（troponin I，TNI）、肝功能损伤指标天冬氨酸转氨酶（aspartate aminotransferase，AST）、丙氨酸转氨酶（alanine aminotransferase，ALT）、肾功能损伤指标血清肌酐（serum creatinine，Scr）、血尿素氮（blood urea nitrogen，BUN）评估器官功能；分别测定肺脏、脑组织的湿质量和干质量，用于计算组织含水量；监测大鼠血压、心率、呼吸频率，记录72 h存活时间及存活率。

结果

与Sham组比较，ESH组大鼠肺脏、肾脏血管以及肠道组织的通透性明显增加（

0.05），肺脏和脑的含水量显著增加（

0.05）；肝、肾、肠道组织血流灌注量分别降低到Sham组的57.1%、39.2%和43.2%（

0.05）；TNI、AST、ALT、Scr和BUN均显著升高（

0.05）；72 h存活时间为（3.8±1.1）h，72 h存活率为0（

0.05）。采用LR复苏，尽管ESH大鼠的通透性降低，器官功能损伤减轻，但与ESH比较，无显著性差异；与ESH+LR组比较，Mdivi-1治疗可明显降低ESH大鼠肺脏、肾脏血管以及肠道组织的通透性和肺脏、脑的含水量（

0.05），其中LR+0.5 mg/kg Mdivi-1治疗效果最好；同时Mdivi-1治疗组可显著增加ESH大鼠的器官灌注，改善器官功能，延长动物的存活时间，提高存活率，其中LR+0.5 mg/kg Mdivi-1治疗组的72 h平均存活时间为55.64 h，72 h存活率为62.5%。

结论

Mdivi-1可降低ESH大鼠肺脏、肾脏和肠道通透性，改善组织灌注，保护心脏、肝脏、肾脏等器官功能，延长存活时间并提高存活率。

Abstract

Objective

To investigate the protective effect of mitochondrial fission inhibitor 1 (Mdivi-1)

on organ function in rats with explosive blast injury combined with hemorrhagic shock.

Methods

A total of 192 SD rats (half male and half female

12 weeks old

weighing about 220 g) were randomly divided into 6 groups: Sham group (only surgical incision along the midline of the abdomen)

model group (ESH group

thermal radiation and shock wave injury followed by femoral artery hemorrhage)

lactated Ringer’s solution resuscitation group (ESH+LR group

LR solution infusion in the femoral vein for resuscitation)

and low-

middle- and high-dose Mdivi-1 groups (0.1

0.5 and 1.0 mg/kg Mdivi-1 intervention after infusion of LR solution). Fluorescent protein tracing was used to determine the leakage amount of fluorescent protein in the lung and kidney tissues to evaluate the vascular permeability. Evans blue dye staining was employed to observe the intestinal permeability and pulmonary vascular permeability. Laser Doppler flowmetry was applied to monitor the tissue blood perfusion in the liver

kidneys

and intestine. Serum levels of cardiac injury marker troponin I (TNI)

liver function markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT)

and renal function markers serum creatinine (Scr) and blood urea nitrogen (BUN) were detected to evaluate the functions of corresponding organs. The water contents of the lungs and brain were calculated by measuring wet weight and dry weight of the lung and brain tissues. Blood pressure

heart rate

and respiratory rate were monitored. The survival time and 72-hour survival rate were recorded and calculated.

Results

Compared with the Sham group

the ESH group exhibited significantly increased vascular permeability in the lungs and kidneys as well as intestinal tissue (

0.05)

along with obviously elevated water contents in the lungs and brain (

0.05)

and decreased blood perfusion in the liver

kidneys

and intestine by 57.1%

39.2%

and 43.2% of the Sham group

respectively (

0.05)

elevated levels of TNI

AST

ALT

Scr and BUN (

0.05)

mean survival time of 3.8±1.1 h

and a 72-hour survival rate of 0 (

0.05). Although LR solution resuscitation reduced vascular permeability and alleviated organ injury in rats with explosive injury combined with hemorrhagic shock

there were no significant differences compared to the ESH group (

0.05). Mdivi-1 treatment notably decreased vascular permeability in the lungs and kidneys and intestine

and water contents in the lungs and brain when compared with the LR group (

0.05)

with the dose of 0.5 mg/kg d

emonstrating the most significant effect. Additionally

Mdivi-1 treatment also significantly enhanced organ perfusion

improved organ functions

prolonged survival time

and increased survival rate. The 0.5 mg/kg treatment resulted in a 72-hour average survival time 55.64 h and a survival rate of 62.5%.

Conclusion

Mitochondrial fission inhibitor Mdivi-1 can reduce the permeabilities in the lungs

kidneys and intestine

improve tissue blood perfusion

protect the organ functions of the heart

liver and kidneys

and finally prolong survival time and increase survival rate in rats with concomitant explosive blast injury and hemorrhagic shock.

关键词

Keywords

references

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