Effect of Capsaicin on Cognitive Function of Rats with Focal Cerebral Ischemia by p38 MAPK/COX-2 Signaling Pathway

CAO Dingyan; BAO Hong; HE Tao; ZHANG Haijun; WU Huanying; CHENG Xiaofeng; MEI Zan

doi:10.13422/j.cnki.syfjx.20222294

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Effect of Capsaicin on Cognitive Function of Rats with Focal Cerebral Ischemia by p38 MAPK/COX-2 Signaling Pathway

更新时间：2022-11-17

- Effect of Capsaicin on Cognitive Function of Rats with Focal Cerebral Ischemia by p38 MAPK/COX-2 Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 24, Pages: 122-130(2022)
- 作者机构：
  
  承德市中心医院，河北承德 067000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20222294
  CLC： R242;R285.5;R966;R259;R743.3
- Received：14 April 2021，
  
  Published Online：11 January 2022，
  
  Published：20 December 2022
- 稿件说明：
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曹定岩,包红,何涛等.辣椒素通过p38 MAPK/COX-2信号通路对局灶性脑缺血大鼠认知功能的影响[J].中国实验方剂学杂志,2022,28(24):122-130.

CAO Dingyan,BAO Hong,HE Tao,et al.Effect of Capsaicin on Cognitive Function of Rats with Focal Cerebral Ischemia by p38 MAPK/COX-2 Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(24):122-130.
曹定岩,包红,何涛等.辣椒素通过p38 MAPK/COX-2信号通路对局灶性脑缺血大鼠认知功能的影响[J].中国实验方剂学杂志,2022,28(24):122-130. DOI： 10.13422/j.cnki.syfjx.20222294.

CAO Dingyan,BAO Hong,HE Tao,et al.Effect of Capsaicin on Cognitive Function of Rats with Focal Cerebral Ischemia by p38 MAPK/COX-2 Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(24):122-130. DOI： 10.13422/j.cnki.syfjx.20222294.

摘要

目的

探讨辣椒素对脑缺血再灌注大鼠认知功能障碍的影响及可能的作用机制。

方法

SD雄性大鼠随机选取12只作为假手术组，其余大鼠采用线栓法复制大脑中动脉阻塞（MCAO）模型。将建模成功的大鼠分为模型组、SB203580［p38丝裂原活化蛋白激酶（p38 MAPK）抑制剂，1 mg·kg

-1

］组、辣椒素低、高剂量（50、100 mg·kg

-1

）组、anisomycin（p38 MAPK激动剂，2 mg·kg

-1

）+辣椒素（100 mg·kg

-1

）组，每组12只。再灌注及给药结束后对大鼠进行神经功能缺陷评分；Morris水迷宫和新型物体识别实验检测大鼠学习和认知能力；苏木素-伊红（HE）染色观察脑组织海马区病理学变化；免疫荧光法检测海马组织小胶质细胞的活化；酶联免疫吸附测定法（ELISA）检测脑组织白细胞介素-1

（IL-1

）、肿瘤坏死因子-

（TNF-

）、前列腺素E

（PGE

）炎性因子的水平；蛋白免疫印迹法（Western blot）检测海马组织瞬时受体电位香草酸亚型1（TRPV1）、p38 MAPK、磷酸化（p）-p38 MAPK、环氧合酶-2（COX-2）蛋白的表达。

结果

与假手术组比较，模型组大鼠神经功能缺损评分、逃避潜伏期、海马CA1区钙结合蛋白-1（Iba-1）阳性表达的小胶质细胞数量、脑组织IL-1

、TNF-

、PGE

水平、海马组织p-p38 MAPK/p38 MAPK、COX-2的表达显著升高（

0.01）；穿越平台位置次数、新颖物体辨别指数（DI）、海马组织TRPV1的表达显著减少（

0.01），且海马神经细胞数量减少，大量炎性细胞浸润；与模型组比较，辣椒素低、高剂量组神经功能缺损评分、逃避潜伏期、海马CA1区Iba-1阳性表达的小胶质细胞数量、脑组织IL-1

、TNF-

、PGE

水平、海马组织p-p38 MAPK/p38 MAPK、COX-2的表达明显降低（

0.05，

0.01）；穿越平台位置次数、DI、TRPV1的表达明显升高（

0.05，

0.01），少量炎性细胞浸润，神经细胞数量明显增多；且使用p38 MAPK的激活剂anisomycin可增加COX-2的表达，明显减弱辣椒素对小胶质细胞活化的抑制作用。

结论

辣椒素对脑缺血再灌注大鼠的认知功能具有保护作用，其作用机制可能与抑制p38 MAPK/COX-2信号通路的激活，进而抑制小胶质细胞的过度活化有关。

Abstract

Objective

To investigate the effect of capsaicin on cognitive dysfunction in rats with cerebral ischemia-reperfusion and its possible mechanism.

Method

Twelve SD male rats were randomly selected as a sham operation group， and the remaining rats were sutured to replicate the model of middle cerebral artery occlusion （MCAO）. The successfully modeled rats were divided into a model group， a SB203580 ［p38 mitogen-activated protein kinase （p38 MAPK） inhibitor， 1 mg·kg

-1

］ group， capsaicin low- and high-dose （50， 100 mg·kg

-1

） groups ， and anisomycin （p38 MAPK agonist， 2 mg·kg

-1

） + capsaicin （100 mg·kg

-1

） group， with 12 rats in each group. After reperfusion and administration， the rats were scored for neurological deficits. Morris water maze and new object recognition experiments were used to test the learning and cognitive abilities of rats. The hematoxylin-eosin （HE） staining was used to observe the pathological changes in the hippocampus of the brain tissue. Immunofluorescence method was used to detect the activation of microglia in the hippocampus. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-1

（IL-1

）， tumor necrosis factor-

（TNF-

）， and prostaglandin E

（PGE

） inflammatory factors in the brain tissue. Western blot was used to determine the protein expression levels of transient receptor potential vanillin subfamily 1 （TRPV1）， p38 MAPK， p-p38 MAPK， and cyclooxygenase-2 （COX-2） in the hippocampal tissue.

Result

As compared with the sham group， the neurological deficit score， escape latency， the number of Iba-1 positive microglia in the hippocampal CA1 area， the IL-1

， TNF-

， and PGE

levels in the brain tissue， and the p-p38 MAPK/p38 MAPK and COX-2 expression in the hippocampus tissue was significantly increased in the model group （

0.01）. In the model group， the number of crossing the platform position， the novel object discrimination index （DI）， and the TRPV1 expression in the hippocampus tissue was significantly reduced （

0.01）， the number of hippocampal nerve cells was reduced， and a large number of inflammatory cells infiltrated. As compared with the model group， the neurological deficit score， escape latency， the number of Iba-1 positive microglia in the hippocampal CA1 area， the IL-1

， TNF-

， and PGE

levels in the hippocampus tissue， and the p-p38 MAPK/p38 MAPK and COX-2 expression in the hippocampus tissue were significantly reduced in the capsaicin low-dose and high-dose groups （

0.05，

0.01）. In the capsaicin low-dose and high-dose groups， the number of crossing the platform position， the DI， and the TRPV1 expression in the hippocampus tissue were significantly increased （

0.05，

0.01）， a small amount of inflammatory cells were infiltrated， and the number of nerve cells was significantly increased. The use of anisomycin， an activator of p38 MAPK， increased the expression of COX-2， and significantly weakened the inhibitory effect of capsaicin on the activation of microglia.

Conclusion

Capsaicin has a protective effect on the cognitive function of rats with cerebral ischemia-reperfusion， and its mechanism may be related to the inhibition of the activation of p38 MAPK/COX-2 signaling pathway， thereby inhibiting the excessive activation of microglia.

关键词

Keywords

references

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