Regulatory effect of nitric oxide scavenger Carboxy-PTIO on PERK/p-eIF2α pathway in rats with transient focal cerebral ischemia

doi:10.3969/j.issn.1006-7795.2019.05.009

Abstract

Abstract: Objective To observe the effect of nitric oxide (NO) remover Carboxy-PTIO (C-PTIO) on cell death mediated by PERK/p-eIF2α pathway in the brain tissues of middle cerebral artery occlusion (MCAO) model rats after 24 hours reperfusion, and to explore the effect of NO production on endoplasmic reticulum stress (ERS)-mediated neuronal apoptosis. Methods Eighteen healthy male Sprague-Dawley rats were divided into sham operation group, MCAO group and MCAO+C-PTIO group (n=6) according to random number table. Rat model of middle cerebral artery ischemia-reperfusion was made by modified suture method, the rats were underwent 90 min of right MCAO, and then reperfusion by withdrawing the filament. The anus temperature of the rats was monitored during the operation. The rats were sacrificed 24 h after reperfusion, and the brain was collected quickly. The expression of p-eIF2α and CHOP in the ischemic penumbra of frozen sections of the brain tissues were detected by immunofluorescence staining. The co-localization of NO-mediated protein damage marker 3-nitrotyrosine (3-NT) with p-eIF2α and CHOP, respectively, was observed with immunofluorescence double labeling. Results 1) No p-eIF2α and 3-NT positive cells were observed in the sham group, while CHOP staining positive cells were occasionally observed. In the MCAO group, the expression of 3-NT, p-eIF2α and CHOP in the ischemic penumbra of the brain tissue increased significantly (P<0.05). 2) Compared with the MCAO group, the expressions of 3-NT, p-eIF2α and CHOP in the penumbra of the ischemia-reperfusion rats were significantly decreased after intraperitoneal injection of C-PTIO (P<0.05). 3) In the penumbra of brain tissue of ischemia-reperfusion rats, 3-NT was co-localized with p-eIF2α and CHOP as observed with immunofluorescence staining. Conclusion NO-mediated oxidative stress damage induces ERS and activates PERK/eIF2α pathway to induce apoptosis during cerebral ischemia-reperfusion. Inhibition of NO production attenuates this process and plays a neuroprotective role.

Key words: cerebral ischemic reperfusion, nitric oxide, endoplasmic reticulum stress, rat, middle cerebral artery occlusion

CLC Number:

R743.32

Huang Yuyou, Fang Yalan, Shi Wenjuan, Liu Kejian, Zhao Yongmei, Ding Mao, Luo Yumin. Regulatory effect of nitric oxide scavenger Carboxy-PTIO on PERK/p-eIF2α pathway in rats with transient focal cerebral ischemia[J]. Journal of Capital Medical University, 2019, 40(5): 709-714.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2019.05.009

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2019/V40/I5/709

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