Mechanism of warmed malate ringer’s solution in fluid resuscitation in improving the lethal triad of severe trauma

WU Yinyu¹; SHE Han; DU Yunxia; ZHANG Yuxi; ZHOU Xiaowei²; LI Qinghui²; LI Tao; HU Yi; MAO Qingxiang; WANG Yaling

doi:10.16016/j.2097-0927.202410036

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Mechanism of warmed malate ringer’s solution in fluid resuscitation in improving the lethal triad of severe trauma

Basic Medicine | 更新时间：2025-02-26

- Mechanism of warmed malate ringer’s solution in fluid resuscitation in improving the lethal triad of severe trauma
- Journal of Army Medical University Vol. 47, Issue 3, Pages: 216-225(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
  3.陆军特色医学中心（第三军医大学大坪医院）：护理部，重庆
- 作者简介：
  
  WANG Yaling， E-mail： hlbwangyl@tmmu.edu.cn
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(82300561);the General Project of Natural Science Foundation of Chongqing(CSTB2023NSCQ-MSX0713);the Joint Medical Research Project for Young Scholars of Chongqing Science and Technology Commission and Chongqing Health Commission(2025QNXM038);the Innovative Leading Talents of Chongqing Talent Program(CSTC2024YCJH-BGZXM0011);the Special Project of Science and Technology Innovation Capacity Promotion of Army Medical University(2023XLC11)
- DOI：10.16016/j.2097-0927.202410036
  CLC： R641;R654.1;R977.8
- Received：12 October 2024，
  
  Revised：03 January 2025，
  
  Published：15 February 2025
- 稿件说明：
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‍吴银雨，佘　汉，杜云霞，等.苹果酸林格液加温液体复苏改善严重创伤致死三联征的机制研究［J］.陆军军医大学学报，2025，47（03）：216-225.DOI：10.16016/j.2097-0927.202410036.

WU Y Y，SHE H，DU Y X，et al.Mechanism of warmed malate ringer’s solution in fluid resusin improving the lethal triad of severe trauma［J］.J Army Med Univ，2025，47（03）：216-225.DOI：10.16016/j.2097-0927.202410036.
‍吴银雨，佘　汉，杜云霞，等.苹果酸林格液加温液体复苏改善严重创伤致死三联征的机制研究［J］.陆军军医大学学报，2025，47（03）：216-225.DOI：10.16016/j.2097-0927.202410036. DOI：

WU Y Y，SHE H，DU Y X，et al.Mechanism of warmed malate ringer’s solution in fluid resusin improving the lethal triad of severe trauma［J］.J Army Med Univ，2025，47（03）：216-225.DOI：10.16016/j.2097-0927.202410036. DOI：

摘要

‍

目的

探讨苹果酸林格液（malate ringer’s solution，MR）加温液体复苏改善严重创伤致死三联征的作用及机制。

方法

SPF级SD大鼠（雌雄各半，体质量200~220 g），采用多发伤联合失血性休克构建大鼠严重创伤模型，以随机数字表法将SD大鼠分为8组（

8）：假手术（Sham）组，仅动静脉置管；严重创伤（trauma，Tra）不同时间点（10、30、60、90、120、180 min）组以及严重创伤（Tra）组，分别于模型建立后不做任何处理观察180 min。通过血栓弹力图检测不同时间点各组大鼠活化凝血时间（activated clotting time，ACT）、凝血反应时间（reaction time，R）、血栓最大振幅（maximum amplitude，MA）、血凝块形成速率（Angle）指标变化，检测大鼠尾部出血时间变化、核心体温变化以及动脉血气相关指标改变情况。检测血浆血管性血友病因子（von Willebrand Factor，vWF）水平、肺静脉内皮线粒体呼吸控制率、血管内皮钙黏蛋白（vascular endothelial cadherin，VE-Cadherin）、过氧化物酶体增殖物激活受体γ共激活因子1α（peroxisome proliferator activating receptor gamma coactivator 1α，PGC1α）、线粒体动力相关蛋白1（dynamin-related protein 1，Drp1）、p-Drp1和线粒体融合蛋白（mitofusin 2，Mfn2）蛋白的表达水平，以评价血管内皮损伤和线粒体功能障碍情况。将SD大鼠按随机数字表法分为3组（

8）：严重创伤后180 min（Tra180 min）组，于创伤后180 min不做任何治疗；MR常温液体复苏（Tra180 min+MR）组，于创伤后60 min时使用医用输血输液加温器常温输注MR进行液体复苏；MR加温液体复苏（Tra180 min+MR+37 ℃）组，于创伤后60 min时使用医用输血输液加温器37 ℃加温输注MR进行液体复苏。观察及检测上述指标，以研究MR的复苏效果。

结果

与Sham组比较，严重创伤大鼠180 min时ACT和R值显著延长（

0.05），MA和Angle值显著缩短（

0.05），尾部出血时间显著延长（

0.05），二氧化碳分压（partial pressure of carbon dioxide，PCO

）、HCO

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=74254466&type=

4.48733330

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=74254484&type=

1.26999998

、剩余碱（ base excess，BE）水平显著降低（

0.05），K

持续升高（

0.05），Na

持续降低（

0.05），Ca

显著降低（

0.05）。此外，与Sham组比较，严重创伤大鼠180 min时血浆vWF水平（

0.05）和肺静脉内皮VE-Cadherin、PGC1α、Mfn2蛋白表达量显著降低（

0.05），p-Drp1表达增强（

0.05），肺静脉内皮线粒体呼吸控制率显著下降（

0.05）。MR液体复苏使大鼠尾部出血时间缩短（

0.05），核心体温升高（

0.05），血浆vWF水平升高（

0.05），VE-Cadherin、PGC1α、和Mfn2蛋白表达量显著升高（

0.05），p-Drp1蛋白表达量显著降低（

0.05），以上结果加温MR液体复苏比常温MR液体复苏效果更显著。

结论

MR加温液体复苏可明显改善严重创伤大鼠致死三联征，这可能与其改善血管内皮细胞线粒体功能减轻血管内皮损伤有关。

Abstract

‍Objective‍　‍

To explore the role and mechanism of warm malate ringer’s solution (MR) in resuscitation of the lethal triad caused by severe trauma.

Methods‍　‍

A rat model of severe trauma was established in SPF-grade SD rats (half male and half female

weighing 200~220 g) using combined multiple injuries and hemorrhagic shock

and the rats were randomly divided into 8 groups (

=8): Sham group

only arterial and venous catheterization; Traum

a (Tra) groups with different time points (10

120

180 min) and a Trauma group that were observed without any treatment for 180 min after model establishment. The changes of activated clotting time (ACT)

reaction time (R)

maximum amplitude (MA)

and rate of blood clot formation (Angle) at different time points were detected by using thromboelastography

and tail bleeding

core body temperature and arterial blood gas parameters

were also observed and detected. The plasma von Willebrand Factor (vWF) level

mitochondrial respiratory control ratio in pulmonary venous endothelium

and expression levels of vascular endothelial cadherin (VE-Cadherin)

peroxisome proliferator activating receptor gamma coactivator 1α (PGC1α)

dynamin-related protein 1 (Drp1)

p-Drp1

and mitofusin 2 (Mfn2) were detected to evaluate the vascular endothelial injury and mitochondrial dysfunction. Another group of SD rats were randomly divided into severe trauma group (no treatment for 180 min after injury)

and MR solution at room temperature and at 37 ℃ groups. MR solution at room temperature or at 37 ℃ was given to the rats using a medical blood transfusion apparatus at 60 min post-trauma. Above indicators were observed and detected to investigate the resuscitation effect of the MR solution.

Results‍　‍

Compared with the Sham group

the severely traumatic rats at 180 min after injury had significantly prolonged ACT and R values (

0.05)

shortened MA and decreased Angle values (

0.05)

extended tail bleeding time (

0.05)

lower partial pressure of carbon dioxide (PCO

) and HCO

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=74254499&type=

4.48733330

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=74254489&type=

1.26999998

and base excess (BE) levels (

0.05)

and continuously increasing K

(

0.05) and decreasing Na

(

0.05) and Ca

levels (

0.05). Additionally

plasma vWF level (

0.05) and protein levels of VE-cadherin

PGC1α and Mfn2 in pulmonary vein endothelium were significantly reduced (

0.05)

the expression of p-Drp1 was enhanced and the mitochondrial respiration control rate was declined in the rats at 180 min after injury (

0.05). MR solution resuscitation shortened tail bleeding time (

0.05)

increased core body temperature (

0.05)

elevated plasma vWF level (

0.05)

increased protein levels of VE-cadherin

PGC1α and Mfn2 (

0.05)

and decreased that of p-Drp1 protein expression (

0.05) when compared with the rats at 180 min after severe traumatic injury. The above effects were more significant in the rats infused with the solution at 37 ℃ than those at room temperature.

Conclusion‍

Warm MR solution significantly improves the lethal triad in rats after severe trauma

which may be associated with its improving mitochondrial function and attenuating vascular endothelial damage.

关键词

Keywords

references

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