Effect of autophagy regulation on vascular dysfunction after traumatic hemorrhagic shock

LEI Yan; PENG Xiao-yong; CHEN Kui-jun; CHENG Xiang-yun; WANG Jian-min; KANG Jian-yi; LI Tao; LIU Liang-ming; YANG Guang-ming

doi:10.11659/jjssx.04E023041

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Effect of autophagy regulation on vascular dysfunction after traumatic hemorrhagic shock

Basic Research | 更新时间：2023-10-23

- Effect of autophagy regulation on vascular dysfunction after traumatic hemorrhagic shock
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 32, Issue 10, Pages: 845-849(2023)
- 作者机构：
  
  1.陆军军医大学陆军卫勤训练基地战救技能训练教研室，重庆 400038
  2.陆军特色医学中心野战外科研究部/创伤烧伤与复合伤国家重点实验室，重庆 400042
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.04E023041
  CLC： R641
- Published：25 October 2023，
  
  Received：11 April 2023，
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雷艳,彭小勇,陈魁君等.调节自噬对创伤性失血休克后血管功能障碍的影响[J].局解手术学杂志,2023,32(10):845-849.

LEI Yan,PENG Xiao-yong,CHEN Kui-jun,et al.Effect of autophagy regulation on vascular dysfunction after traumatic hemorrhagic shock[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2023,32(10):845-849.
雷艳,彭小勇,陈魁君等.调节自噬对创伤性失血休克后血管功能障碍的影响[J].局解手术学杂志,2023,32(10):845-849. DOI： 10.11659/jjssx.04E023041.

LEI Yan,PENG Xiao-yong,CHEN Kui-jun,et al.Effect of autophagy regulation on vascular dysfunction after traumatic hemorrhagic shock[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2023,32(10):845-849. DOI： 10.11659/jjssx.04E023041.

摘要

目的

研究自噬对创伤性失血休克（THS）后血管功能障碍的影响。

方法

80只SD大鼠随机分为对照组、休克组、休克+自噬抑制剂3-甲基腺嘌呤（3-MA）1、2、4 mmol/L组、休克+自噬激动剂雷帕霉素（RAPA）0.1、1、2、10 μmol/L组、休克+RAPA（1 μmol/L）+3-MA（2 mmol/L）组，建立THS大鼠模型，观察上调或抑制自噬对THS大鼠血管反应性的影响。24只大鼠随机分为正常组、休克+乳酸林格氏液（LR）组、休克+LR+RAPA组，在体观察诱导自噬对休克大鼠平均动脉血压（MAP）及血流灌注的影响，同时检测血管组织中自噬标志物相关蛋白的表达。

结果

离体血管功能检测结果显示，THS大鼠的血管反应性明显降低，RAPA处理可提高THS大鼠的血管反应性，而3-MA处理可使THS大鼠血管反应性进一步降低，并且可拮抗RAPA提高THS大鼠血管反应性的作用。在整体动物水平，THS大鼠在给予2倍失血量的LR复苏后，MAP和肝、肾血流灌注有所恢复，但仍显著低于正常大鼠；预先给予RAPA的THS大鼠在经LR复苏后，MAP和肝、肾血流灌注均得到了明显恢复，其效果明显优于单纯LR治疗。Western blot检测结果显示，休克+LR组大鼠血管组织中自噬标志物LC3-Ⅱ/LC3-Ⅰ和Beclin-1/β-actin水平低于正常组大鼠，而RAPA处理升高了休克后以上标志物的水平。

结论

自噬与THS后血管功能障碍的发生密切相关，上调自噬可提高休克血管反应性和血流灌注，从而改善创伤休克血管功能。

Abstract

Objective

To investigate the effect of autophagy on vascular dysfunction after traumatic hemorrhagic shock （THS）.

Methods

A total of 80 SD rats were randomly divided into the control group，shock group，shock+the autophagy inhibitor 3-methyladenine （3-MA） of 1，2，4 mmol/L groups，shock+the autophagy inducer rapamycin （RAPA） of 0.1，1，2，10 μmol/L groups，and shock+RAPA（1 μmol/L）+3-MA（2 mmol/L） group.The rat model of THS was established to observe the effect of upregulation or inhibition of autophagy on the vascular reactivity of THS rats.A total of 24 rats were randomly divided into the normal group，shock+lactated Ringer´s solution （LR） group，and shock+LR+RAPA group，and the effects of induced autophagy on mean arterial pressure （MAP） and organ blood perfusion of THS rats were observed in vivo，and the expression of autophagy marker-related proteins in vascular tissues were detected.

Results

The results of the vascular function experiment in vitro showed that the vascular reactivity of THS rats was signiﬁcantly decreased，and RAPA treatment could improve the vascular reactivity of THS rats

while 3-MA treatment could further reduce the vascular reactivity of THS rats

which could also antagonize the effect of RAPA on improving vascular reactivity in THS rats.At the overall animal level

the MAP and blood perfusion of liver and kidney of THS rats were restored after giving LR resuscitation with the amount of twice as much as blood loss

while which were still significantly lower than those of the normal rats.After LR resuscitation

the MAP and blood perfusion of liver and kidney were significantly restored of THS rats with pretreated with RAPA

whose effect was significantly better than that with single LR treatment.Western blot revealed that the levels of LC3-Ⅱ/LC3-Ⅰ and Beclin-1/β-actin in vessel tissue from THS rats in the shock+LR group were lower than those of rats in the normal group

while RAPA treatment increased the levels of the above markers after shock.

Conclusion

Autophagy is closely related to the occurrence of vascular dysfunction after THS

and upregulation of autophagy can improve the reactivity and blood perfusion of shock vessel

thereby improving the function of traumatic shock vessel.

关键词

自噬创伤性失血休克血管反应性雷帕霉素3-甲基腺嘌呤血流灌注

Keywords

autophagytraumatic hemorrhagic shockvascular reactivityrapamycin3-methyladenineblood perfusion

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