高原、高寒、高热环境下致死性休克大鼠模型的建立与标准化造模方式筛选

吴跃; 朱娱; 李清晖; 李涛

doi:10.16016/j.2097-0927.202511007

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高原、高寒、高热环境下致死性休克大鼠模型的建立与标准化造模方式筛选

基础医学 | 更新时间：2026-01-14

- 高原、高寒、高热环境下致死性休克大鼠模型的建立与标准化造模方式筛选
- Establishment and standardized modeling of lethal shock rat models in high-altitude, high-cold, and high-heat environments
- 陆军军医大学学报 2026年48卷第1期页码：63-74
- 作者机构：
  
  陆军军医大学（第三军医大学）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：
  
  李涛，E-mail：lt200132@tmmu.edu.cn
- 基金信息：
  
  重庆市教委科学技术研究项目(KJZD-K202512803);国家自然科学基金青年基金项目(82402549)
- DOI：10.16016/j.2097-0927.202511007
  中图分类号： R332;R339.5;R605.971
- 收稿：2025-11-02，
  
  修回：2025-12-05，
  
  录用：2025-12-15，
  
  纸质出版：2026-01-15
- 稿件说明：
移动端阅览
吴跃，朱娱，李清晖，等.高原、高寒、高热环境下致死性休克大鼠模型的建立与标准化造模方式筛选［J］.陆军军医大学学报，2026，48（01）：63-74.DOI：10.16016/j.2097-0927.202511007.

WU Y，ZHU Y，LI Q H，et al.Establishment and standardized modeling of lethal shock rat models in high-altitude， high-cold， and high-heat environments［J］.J Army Med Univ，2026，48（01）：63-74.DOI：10.16016/j.2097-0927.202511007.
吴跃，朱娱，李清晖，等.高原、高寒、高热环境下致死性休克大鼠模型的建立与标准化造模方式筛选［J］.陆军军医大学学报，2026，48（01）：63-74.DOI：10.16016/j.2097-0927.202511007. DOI：

WU Y，ZHU Y，LI Q H，et al.Establishment and standardized modeling of lethal shock rat models in high-altitude， high-cold， and high-heat environments［J］.J Army Med Univ，2026，48（01）：63-74.DOI：10.16016/j.2097-0927.202511007. DOI：

摘要

目的

基于本实验室已建立的常规环境大鼠失血性休克模型，建立高原、高寒、高热特殊环境大鼠致死性休克模型，为特殊环境下致死性休克救治相关研究提供动物模型。

方法

864只12周龄、体质量（200±20）g SPF级雄性SD大鼠按不同预处理环境分为4组（

=216）：高原环境组［低压氧舱模拟4 000 m海拔，（22±2）℃暴露48 h］；高寒环境组（海拔200~300 m，-20 ℃暴露6 h）；高热环境组（海拔200~300 m，35 ℃暴露12 h），常规环境对照组（不做环境预处理）。环境预处理后，采用4种脾损伤方式诱导腹腔自由出血制备非控制性失血性休克模型：①距脾实质末端3 cm处离断；②距脾实质末端3 cm和5 cm处分别离断；③脾尾端小动脉分支离断；④脾尾端小动脉分支离断联合距脾实质末端3 cm处离断，直至平均动脉压（mean arterial pressure，MAP）降至40 mmHg即判定模型制备成功。模型成功后，用乳酸林格氏液（lactated Ringer’s solution，LR）低压维持MAP在50~60 mmHg 1 h，经脾动脉结扎彻底止血后，按出血量2倍体积LR进行确定性复苏。监测MAP、呼吸频率（respiratory rate，RR）、心率（heart rate，HR），检测心功能［肌钙蛋白I（troponin I， TnI）］、肝功能［谷草转氨酶（aspartate aminotransferase，AST）、谷丙转氨酶（alanine aminotransferase， ALT）］、肾功能［血尿素氮（blood urea nitrogen， BUN）、血清肌肝（serum creatinine，Scr）］，观察大鼠存活时间及6 h存活率，筛选各环境适配的造模方式。用各环境组筛选出的造模方式分别在相应环境预处理的巴马香猪上制备失血性休克模型，并按前述治疗方案确定性复苏后，观察巴马香猪基础生理指标（MAP、RR、HR）、器官功能（心、肝、肾）及存活情况，以验证造模方式稳定性。

结果

不同环境致死性休克模型的适配造模方式存在差异：常规环境优选重度血管联合实质损伤的方式④，高原环境优选重度血管损伤的方式③，高寒环境优选轻度实质损伤的方式①，高热环境优选中度双位点实质损伤的方式②，上述方式均满足休克后6 h致死率

70%、低压复苏后失血量

50%、确定性复苏后存活率

50%的模型标准。休克状态下，各组大鼠MAP显著降低（

0.001），RR、HR异常改变，心、肝、肾器官功能指标（TnI、AST、ALT、BUN、Scr）显著升高（

0.05），存活时间缩短；经LR低压复苏联合确定性复苏后，MAP显著回升（

0.01），器官功能指标显著改善，存活时间延长。巴马香猪验证结果显示：休克组MAP降至约40 mmHg，RR显著降低，HR升高，6 h存活率为0，心、肝、肾器官功能指标（TnI、AST、ALT、BUN、Scr）显著升高（

0.001）；复苏组MAP显著升高至58.6~68.4 mmHg（

0.01），器官功能明显改善，6 h存活率达50.00%~56.25%，模型可靠性得到确认。

结论

成功建立了高原、高寒、高热环境下致死性休克模型，明确了各环境对应的标准化造模方式；经巴马香猪验证，模型稳定性与可靠性符合实验要求。

Abstract

Objective

To establish lethal shock models in high-altitude

high-cold

and high-heat environments based on the conventional environment hemorrhagic shock (HS) model established in our laboratory

in order to provide animal models for lethal shock treatment in special environments.

Methods

A total of 864 SPF-grade male SD rats (12 weeks old

weighing 200±20 g) were divided into high-altitude environment group (simulated 4 000 m altitude in a low-pressure oxygen chamber

exposed to 22±2 ℃ for 48 h)

high-cold environment group (altitude 200 to 300 m

exposure to -20 ℃ for 6 h)

high-heat environment group (altitude 200 to 300 m

exposure to 35 ℃ for 12 h)

and conventional environment control group (no environmental pretreatment) according to different environmental pretreatment

with 216 animals in each group. After environmental pre-conditioning

4 types of spleen injury methods were used to induce free intra-abdominal bleeding to construct corresponding uncontrolled HS model. The injury methods were as follows: ① Transverse transection at 3 cm away from the end of the splenic parenchyma; ② Transverse transection separately at 3 and 5 cm away from the end of the splenic parenchyma; ③ Transverse arteriotomy of a small arterial branch at the splenic tail; ④ Transverse arteriotomy of a small arterial branch at the splenic tail combined with transection at 3 cm away from the end of the splenic parenchyma. Free intra-abdominal bleeding was induced by above 4 methods until the mean arterial pressure (MAP) dropped to 40 mmHg

which was defined as successful establishment of the uncontrolled HS model. After successful modeling

lactated Ringer’s (LR) solution was employed to maintain MAP at 50 to 60 mmHg at low pressure for 1 h. After the splenic artery was ligated for complete hemostasis

definitive resuscitation was obtained with LR solution of 2×blood loss volume. MAP

respiratory rate (RR) and heart rate (HR) were monitored

cardiac function [troponin I (TnI)]

liver function [aspartate aminotransferase （AST）， alanine aminotransferase（ALT）］、and renal function ［blood urea nitrogen （BUN）， serum creatinine （Scr）］ were evaluated

survival time was observed

and 6-hour survival rate was calculated to screeen the appropriate modeling methods for each environment. Then the obtained modeling methods were applied on Bama pigs to establish HS models for high-altitude

high-cold

and high-heat environments

respectively. After modelling

the pigs were resuscitated according to the aforementioned treatment regimens

and basic physiological indicators (MAP

HR)

organ functions (heart

liver

kidney)

and survival status were observed to verify the stability of the modeling methods.

Results

There were differences in the appropriate modeling methods for different environments: the conventional environment preferred method ④

the high-altitude environment preferred method ③

the high-cold environment preferred method ①

and the high-heat environment preferred method ②. All the above methods met the model standards of a 6-hour mortality rate

70% after shock

a blood loss

50% after low-pressure resuscitation

and a survival rate

50% after definitive resuscitation. In the state of shock

the MAP of rats was significantly reduced in each group (

0.001)

RR and HR were abnormally changed

the indicators of cardiac

liver

and renal functions (TnI

AST

ALT

BUN

Scr) (

0.05) were significantly increased

and the survival time was obviously shortened. After LR low-pressure resuscitation combined with definitive resuscitation

the MAP was notably recovered (

0.01)

the organ function indicators were significantly improved

and the survival time was greatly prolonged. The verification results in Bama miniature pigs showed that

in the shock group

MAP was decreased to approximately 40 mmHg

RR was significantly reduced

HR was increased

the 6-hour survival rate was 0%

and the indicators of cardiac

liver

and renal functions (TnI

AST

ALT

BUN

and Scr) were notbly elevated (

0.001). In the resuscitation group

the MAP was significantly increased to 58.6 to 68.4 mmHg (

0.01)

the 6-hour survival rate reached 50.00% to 56.25%

and organ functions were significantly improved. All these findings confirmed the reliability of each model.

Conclusion

Lethal shock models under high-altitude

high-cold

and high-heat environments are successfully established

respectively

and the appropriate standardized modeling methods are identified for each environment. The modelling methods are further verified on Bama miniature pigs

and the constructed models have advantages of stability and reliability for laboratory requirements.

关键词

Keywords

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