Senp1介导蛛网膜下腔出血后神经元焦亡的作用

马寅瑞; 何朝晖

doi:10.16016/j.2097-0927.202401084

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Senp1介导蛛网膜下腔出血后神经元焦亡的作用

基础医学 | 更新时间：2026-01-09

- Senp1介导蛛网膜下腔出血后神经元焦亡的作用
- Senp1 mediates neuronal pyroptosis after subarachnoid hemorrhage in mice
- 陆军军医大学学报 2024年46卷第17期页码：1976-1984
- 作者机构：
  
  400016 重庆，重庆医科大学附属第一医院神经外科
- 作者简介：
  
  [何朝晖，E-mail：geno_he@163.com HE Zhaohui, E-mail: geno_he@163.com
- 基金信息：
  
  ‍国家自然科学基金面上项目(81870927);重庆市自然科学基金面上项目(CSTB2023NSCQ-MSX0112)
- DOI：10.16016/j.2097-0927.202401084
  中图分类号： R345;R363.21;R743.35
- 收稿：2024-01-21，
  
  修回：2024-03-24，
  
  纸质出版：2024-09-15
- 稿件说明：
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马寅瑞, 何朝晖. Senp1介导蛛网膜下腔出血后神经元焦亡的作用[J]. 陆军军医大学学报, 2024,46(17):1976-1984.

Yinrui MA, Zhaohui HE. Senp1 mediates neuronal pyroptosis after subarachnoid hemorrhage in mice[J]. Journal of Army Medical University, 2024, 46(17): 1976-1984.
马寅瑞, 何朝晖. Senp1介导蛛网膜下腔出血后神经元焦亡的作用[J]. 陆军军医大学学报, 2024,46(17):1976-1984. DOI： 10.16016/j.2097-0927.202401084.

Yinrui MA, Zhaohui HE. Senp1 mediates neuronal pyroptosis after subarachnoid hemorrhage in mice[J]. Journal of Army Medical University, 2024, 46(17): 1976-1984. DOI： 10.16016/j.2097-0927.202401084.

摘要

目的

探究SUMO特异性蛋白酶1(SUMO-specific protease 1，Senp1)在蛛网膜下腔出血(subarachnoid hemorrhage，SAH)中参与神经元焦亡的机制。

方法

95只6~8周龄雄性C57BL/6小鼠采用随机数字表法分为假手术(sham)组(

=15)、SAH(6、12、24、48、72 h)组(

=8、7、17、6、6)、SAH+AAV9-NC组(

=19)、SAH+AAV9-sh-Senp1组(

=17)，左侧颈内动脉血管内穿刺建立SAH动物模型，神经行为学评分评价神经功能，HE染色、FJC染色观察脑皮质神经元损伤情况，RT-PCR检测敲低Senp1的mRNA水平，Western blot检测各组Senp1、NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3

NLRP3)、焦孔素D(gasdermin D，GSDMD)、含PYD和CARD域蛋白(PYD and CARD domain containing，ASC)及半胱氨酸蛋白酶-1(Caspase-1)的表达，免疫荧光观察Senp1和NLRP3的定位表达。

结果

SAH后Senp1表达升高，于24 h达到峰值，并表达于脑皮质神经元。与sh

am组相比，SAH组Senp1、NLRP3、GSDMD、ASC和Caspase-1的表达明显升高(

0.01)，神经损伤加重，并且有神经功能障碍；与SAH+AAV9-NC组相比，给予AAV9-sh-Senp1后神经损伤及功能明显改善，Senp1及上述焦亡蛋白NLRP3、GSDMD、ASC、Caspase-1表达明显降低(

0.01)，抑制了NLRP3介导的神经元焦亡。

结论

Senp1在SAH后促进细胞焦亡的发生，介导神经元损伤。

Abstract

Objective

To investigate the mechanism of SUMO-specific protease 1 (Senp1) involved in neuronal pyroptosis in subarachnoid hemorrhage (SAH).

Methods

A total of 95 male C57BL/6 mice (6~8 weeks old) were randomly divided into sham group (

=15)

SAH groups (for 6

48 and 72 h

respectively

6 and 6)

SAH+AAV9-NC group (

=19)

and SAH+AAV9-sh-Senp1 group (

=17). Mouse model of SAH was established by intravascular puncture in the left internal carotid artery. Neurobehavioral scoring was used to evaluate neurological function

HE staining and FJC staining were employed to observe brain injury

RT-PCR was conducted to detect the knockdown of Senp1

Western blotting was applied to measure the expression of Senp1

NOD-like receptor thermal protein domain associated protein 3 (NLRP3)

gasdermin D (GSDMD)

PYD and CARD domain containing (ASC) and Caspase-1

and immunofluorescence assay was performed to observe the locations of Senp1 and NLRP3.

Results

SAH caused the elevated expression of Senp1

which reached a peak in 24 h and located in the cortical neurons. Compared with the sham group

the expression of Senp1

NLRP3

GSDMD

ASC and Caspase-1 were significantly enhanced in the SAH groups (

0.01)

with aggravation of nerve injury and neurological deficits. Administration of AAV9-sh-Senp1 resulted in significantly improved nerve injury and function

decreased expression of above proteins (

0.01)

and inhibited neuron pyroptosis when compared

with the SAH+AAV9-NC group.

Conclusion

Senp1 promotes the occurrence of neuronal pyroptosis and mediates neuronal injury after SAH.

关键词

Keywords

references

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