Protective effects of mitochondrial fission inhibitor, Mdivi-1, on traumatic shock rats at high altitude

Yue WU; Yu ZHU; Yuanqun ZHOU; Qinghui LI; Xiaoyong PENG; Xinming XIANG; Liangming LIU; Tao LI

doi:10.16016/j.2097-0927.202205040

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Protective effects of mitochondrial fission inhibitor, Mdivi-1, on traumatic shock rats at high altitude

Monographic Reports: Treatment of war wound and traumatic shock | 更新时间：2026-01-09

- Protective effects of mitochondrial fission inhibitor, Mdivi-1, on traumatic shock rats at high altitude
- Journal of Army Medical University Vol. 44, Issue 20, Pages: 2030-2036(2022)
- 作者机构：
  
  400042 重庆，陆军特色医学中心战伤休克与输血研究室，创伤、烧伤与复合伤国家重点实验室
- 作者简介：
- 基金信息：
  
  the Key Logistic Scientific Project of the "Thirteenth Five-year Plan" of Medical Research of PLA(AWS16J032);the Key Project of Logistic Scientific Research Plan of PLA(BLJ19J008)
- DOI：10.16016/j.2097-0927.202205040
  CLC： R339.54;R605.971;R977.9
- Received：10 May 2022，
  
  Revised：2022-07-15，
  
  Published：30 October 2022
- 稿件说明：
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Yue WU, Yu ZHU, Yuanqun ZHOU, et al. Protective effects of mitochondrial fission inhibitor, Mdivi-1, on traumatic shock rats at high altitude[J]. Journal of Army Medical University, 2022, 44(20): 2030-2036.
DOI：

Yue WU, Yu ZHU, Yuanqun ZHOU, et al. Protective effects of mitochondrial fission inhibitor, Mdivi-1, on traumatic shock rats at high altitude[J]. Journal of Army Medical University, 2022, 44(20): 2030-2036. DOI： 10.16016/j.2097-0927.202205040.

摘要

目的

观察线粒体分裂抑制剂(mitochondrial division inhibitor-1，Mdivi-1)对高原战创伤休克的早期救治作用。

方法

SD大鼠从平原(重庆)急进(空运)至高原(拉萨，海拔3 600 m)72 h后，通过脾动脉离断自由出血至平均动脉血压(mean arterial pressure，MAP)降至40 mmHg，建立高原战创伤休克模型。实验分为假手术组、休克组、乳酸林格氏液(Lactate Ringer’s，LR)对照组、0.1和0.5 mg/kg Mdivi-1组。实验分两部分，第一部分大鼠不接受止血处理，仅采用LR或联合0.1、0.5 mg/kg Mdivi-1进行复苏，将MAP维持在50~60 mmHg，观察大鼠血压、失血量、输液量以及存活的变化；第二部分低压复苏1 h后，经彻底止血后进行确定性复苏，观察大鼠失血量、输液量、器官功能、组织氧分压、肺脑含水量以及动物存活情况的变化。

结果

在不进行止血处理时，采用LR进行低压复苏，大鼠MAP可维持在50~60 mmHg约1 h。而后增加液体输入量，MAP不升高反而进行性降低，且失血量明显增加。Mdivi-1联合低压复苏能将MAP较好地维持在50~60 mmHg约3 h；与LR对照组相比，大鼠失血量、输液量显著减少。低压复苏1 h、行止血及确定性治疗后，单纯LR复苏大鼠的组织氧分压仍在较低水平，同时肺脑含水量增加，重要器官如心、肝和肾脏功能受损严重；而给予0.1或0.5 mg/kg Mdivi-1后大鼠的组织氧分压明显提高，肺脑含水量降低，心、肝和肾脏功能受损明显减轻，与LR对照组相比，大鼠存活明显延长。

结论

Mdivi-1适用于高原战创伤休克的早期救治，可改善器官功能，延长黄金救治时间窗。

Abstract

Objective

To observe the early therapeutic effects of a mitochondrial fission inhibitor

mitochondrial division inhibitor 1 (Mdivi-1)

on the traumatic shock rats at high altitude.

Methods

SD rats were rapidly transported (airlift) from the plain (Chongqing) to the plateau (Lhasa

3 600 m altitude). After 72 h

the traumatic shock model of rats at high altitude was prepared by free bleeding from splenic artery disconnection until mean arterial pressure (MAP) fell to 40 mmHg. The animals were divided into 5 groups: sham-operation group

shock group

Lactate Ringer's (LR) solution control group

and LR combined with 0.1 and 0.5 mg/kg Mdivi-1 groups. Then the experiments were designed as 2 parts. The rats in the first part were resuscitated with mere LR solution or combined with 0.1 or 0.5 mg/kg Mdivi-1 without hemostatic treatment. With the MAP maintained at 50-60 mmHg

the changes of MAP

bleeding volume

fluid infusion volume and survival rate were observed in each group. In the second part

bleeding control was performed by ligation of the spleen artery after 1 h of low-pressure resuscitation

and definitive resuscitation was continuously given. The changes of blood loss

infusion volume

organ functions

tissue oxygen partial pressure

lung and brain water content and animal survival were subsequently investigated.

Results

When LR solution was used for low-pressure resuscitation without hemostatic treatment

the MAP of rats was maintained at 50-60 mmHg for about 1 h

and then began to drop gradually rather than rise after increasing the amount of fluid input

with the bleeding volume soared obviously. Whereas Mdivi-1 combination treatment maintained MAP at 50-60 mmHg for about 3 h

and significantly reduced the bleeding volume and fluid infusion. Further studies showed that in the hemostatic resuscitation treatment

the rats of the LR control group still had a rather low level of tissue oxygen partial pressure

with elevated water contents in the lung and brain

and seriously impaired functions of vital organs such as the heart

liver and kidney. However

Mdivi-1 (0.1 or 0.5 mg/kg) treatment remarkably improved the damage

increased the tissue oxygen partial pressure

reduced the water contents in the lung and brain

alleviated the impairment of the heart

liver and kidney

and greatly prolonged the survival time of shock animals.

Conclusion

Mdivi-1 is suitable for the early treatment of traumatic shock at high altitude

which can improve organ functions and extend the golden time of treatment.

关键词

Keywords

references

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