五味子乙素抑制NLRP3炎性体通路减轻大鼠蛛网膜下腔出血早期脑损伤

Song CHEN; Yi-hang DING; Song-sheng SHI; Xian-kun TU

doi:10.1007/s11655-021-3348-z

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五味子乙素抑制NLRP3炎性体通路减轻大鼠蛛网膜下腔出血早期脑损伤

Original Article | Updated：2022-06-27

- 五味子乙素抑制NLRP3炎性体通路减轻大鼠蛛网膜下腔出血早期脑损伤
- Schisandrin B Inhibits NLRP3 Inflammasome Pathway and Attenuates Early Brain Injury in Rats of Subarachnoid Hemorrhage
- Chinese Journal of Integrative Medicine 2022年28卷第7期页码：594-602
- Affiliations：
  
  Department of Neurosurgery, Fujian Medical University Union Hospital, Neurosurgery Research Institute of Fujian Province,Fuzhou (350001), China
- Author bio：
  
  Dr. TU Xian-kun, E-mail: unionnstu@hotmail.com
- Funds：
  
  the Natural Science Foundation of Fujian Province of China(2020J011016);the Joint Funds for the Innovation of Science and Technology of Fujian Province(2018Y9004);the Startup Fund for Scientific Research of Fujian Medical University(2019QH1055)
- DOI：10.1007/s11655-021-3348-z
  中图分类号：
- 纸质出版日期：2022-07-01，
  
  网络出版日期：2022-01-11，
  
  录用日期：2021-09-17
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Song CHEN, Yi-hang DING, Song-sheng SHI, 等. 五味子乙素抑制NLRP3炎性体通路减轻大鼠蛛网膜下腔出血早期脑损伤[J]. Chinese Journal of Integrative Medicine, 2022,28(7):594-602.

Song CHEN, Yi-hang DING, Song-sheng SHI, et al. Schisandrin B Inhibits NLRP3 Inflammasome Pathway and Attenuates Early Brain Injury in Rats of Subarachnoid Hemorrhage[J]. Chinese Journal of Integrative Medicine, 2022,28(7):594-602.
Song CHEN, Yi-hang DING, Song-sheng SHI, 等. 五味子乙素抑制NLRP3炎性体通路减轻大鼠蛛网膜下腔出血早期脑损伤[J]. Chinese Journal of Integrative Medicine, 2022,28(7):594-602. DOI： 10.1007/s11655-021-3348-z.

Song CHEN, Yi-hang DING, Song-sheng SHI, et al. Schisandrin B Inhibits NLRP3 Inflammasome Pathway and Attenuates Early Brain Injury in Rats of Subarachnoid Hemorrhage[J]. Chinese Journal of Integrative Medicine, 2022,28(7):594-602. DOI： 10.1007/s11655-021-3348-z.

摘要

目的:

探讨五味子乙素 (schisandrin

Sch B) 减轻大鼠蛛网膜下腔出血 (subarachnoid hemorrhage

SAH) 早期脑损伤的作用机制.

方法:

用随机分配的方法将SD大鼠分为4组: 假手术组、SAH组、SAH+溶媒组、SAH+五味子乙素组. 通过血管内穿刺法制作大鼠蛛网膜下腔出血模型

制作模型后2小时和12小时分别给予Sch B (100mg/kg) 或生理盐水

然后在24小时进行SAH评分、神经功能评分、脑水肿程度、EB含量、TUNEL染色等实验. 并通过免疫荧光染色检测Iba-1和MPO的表达情况

用Western blot检测Bcl-2、Bax、Caspase-3、NLRP3、ASC、Caspase-1和IL-1β和IL-18的表达情况.

结果:

与SAH组相比

Sch B可明显改善大鼠的神经功能情况、减轻脑水肿和血脑屏障破坏程度、并抑制神经元凋亡 (

0.05或

0.01) . Sch B可下调Iba-1和MPO的表达 (

0.01)

Sch B抑制Bax、Caspase-3、NLRP3、ASC、Caspase-1和IL-1β和IL-18的表达 (

0.01)

此外

Sch B上调Bcl-2的表达 (

0.01) .

结论:

Sch B可减轻SAH诱导的早期脑损伤

这可能与Sch B抑制神经炎症反应、神经元凋亡和对NLRP3炎性体通路的抑制作用有关.

Abstract

Objective:

To determine whether Schisandrin B (Sch B) attenuates early brain injury (EBI) in rats with subarachnoid hemorrhage (SAH).

Methods:

Sprague-Dawley rats were divided into sham (sham operation)

SAH

SAH+vehicle

and SAH+Sch B groups using a random number table. Rats underwent SAH by endovascular perforation and received Sch B (100 mg/kg) or normal saline after 2 and 12 h of SAH. SAH grading

neurological scores

brain water content

Evan's blue extravasation

and terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining were carried out 24 h after SAH. Immunofluorescent staining was performed to detect the expressions of ionized calcium binding adapter molecule 1 (Iba-1) and myeloperoxidase (MPO) in the rat brain

while the expressions of B-cell lymphoma 2 (Bcl-2)

Bax

Caspase-3

nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3)

apoptosis-associated specklike protein containing the caspase-1 activator domain (ASC)

Caspase-1

interleukin (IL)-1β

and IL-18 in the rat brains were detected by Western blot.

Results:

Compared with the SAH group

Sch B significantly improved the neurological function

reduced brain water content

Evan's blue content

and apoptotic cells number in the brain of rats (

0.05 or

0.01). Moreover

Sch B decreased SAH-induced expressions of Iba-1 and MPO (

0.01). SAH caused the elevated expressions of Bax

Caspase-3

NLRP3

ASC

Caspase-1

IL-1β

and IL-18 in the rat brain (

0.01)

all of which were inhibited by Sch B (

0.01). In addition

Sch B increased the Bcl-2 expression (

0.01).

Conclusion:

Sch B attenuated SAH-induced EBI

which might be associated with the inhibition of neuroinflammation

neuronal apoptosis

and the NLRP3 inflammatory signaling pathway.

关键词

Keywords

schisandrin Bsubarachnoid hemorrhageearly brain injuryinflammationneuronal apoptosisnucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3Chinese medicine

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