Effect of Capsaicin on Cognitive Function of Rats with Focal Cerebral Ischemia by p38 MAPK/COX-2 Signaling Pathway
10.13422/j.cnki.syfjx.20222294
- VernacularTitle: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
- Author:
Dingyan CAO
1
;
Hong BAO
1
;
Tao HE
1
;
Haijun ZHANG
1
;
Huanying WU
1
;
Xiaofeng CHENG
1
;
Zan MEI
1
Author Information
1. Chengde Central Hospital，Chengde 067000，China
- Publication Type:Journal Article
- Keywords:
capsaicin;
cerebral ischemia-reperfusion;
cognitive dysfunction;
p38 mitogen-activated protein kinase/cyclooxygenase 2 signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(24):122-130
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect of capsaicin on cognitive dysfunction in rats with cerebral ischemia-reperfusion and its possible mechanism. MethodTwelve 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-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and prostaglandin E2 （PGE2） 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. ResultAs 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-1β， TNF-α， and PGE2 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 （P<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 （P<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-1β， TNF-α， and PGE2 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 （P<0.05，P<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 （P<0.05，P<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. ConclusionCapsaicin 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.
