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在大鼠手术性脑损伤模型中,PERK通路对神经元凋亡的可能机制。

Possible mechanisms of the PERK pathway on neuronal apoptosis in a rat model of surgical brain injury.

作者信息

Wu Mu-Yao, Gao Fan, Tang Jia-Feng, Shen Jin-Chao, Gao Rong, Dang Bao-Qi, Chen Gang

机构信息

Department of Rehabilitation, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine Suzhou, China.

Anesthesiology Department, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine Suzhou, China.

出版信息

Am J Transl Res. 2021 Feb 15;13(2):732-742. eCollection 2021.

Abstract

Protein kinase R-like endoplasmic reticulum kinase (PERK) is an important transmembrane protein in the endoplasmic reticulum (ER). PERK signaling has a critical function in neuronal apoptosis. This work aimed to assess PERK signaling for its function in surgical brain injury (SBI) and to explore the underlying mechanisms. Totally 120 male Sprague Dawley (SD) rats were assessed in an SBI model. The effects of the PERK inhibitor GSK2606414 were examined by Western-blot, immunofluorescent staining, TUNEL staining, fluoro-jade C (FJC) staining and neurological assays in rats with SBI. In this study, p-PERK and p-eIF2α protein amounts were increased upon SBI establishment, peaking at 24 h. Meanwhile, administration of GSK2606414 reversed these effects and prevented neuronal apoptosis. The PERK pathway has a significant function in neuronal apoptosis, and its suppression after SBI promotes the alleviation of brain injury. This suggests that targeting the PERK signaling pathway may represent an efficient therapeutic option for improving prognosis in SBI patients.

摘要

蛋白激酶R样内质网激酶(PERK)是内质网(ER)中的一种重要跨膜蛋白。PERK信号传导在神经元凋亡中起关键作用。这项工作旨在评估PERK信号传导在手术性脑损伤(SBI)中的功能,并探索其潜在机制。总共120只雄性Sprague Dawley(SD)大鼠在SBI模型中进行评估。通过蛋白质免疫印迹法、免疫荧光染色、TUNEL染色、荧光玉髓C(FJC)染色和神经学检测,研究了PERK抑制剂GSK2606414对SBI大鼠的影响。在本研究中,SBI建立后p-PERK和p-eIF2α蛋白量增加,在24小时达到峰值。同时,给予GSK2606414可逆转这些效应并防止神经元凋亡。PERK通路在神经元凋亡中具有重要作用,SBI后对其抑制可促进脑损伤的减轻。这表明靶向PERK信号通路可能是改善SBI患者预后的有效治疗选择。

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