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MRPL41 作为针灸的靶点,通过激活 p53 通路促进缺血性中风模型中的神经元凋亡。

MRPL41, as a target for acupuncture, promotes neuron apoptosis in models of ischemic stroke via activating p53 pathway.

机构信息

Department of Rehabilitation, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Department of Orthopedics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

出版信息

Neurochem Int. 2024 Nov;180:105881. doi: 10.1016/j.neuint.2024.105881. Epub 2024 Oct 13.

Abstract

Neuronal death is the key cause of ischemic stroke. Acupuncture (Acu) is a recognized method for the treatment and amelioration of cerebral ischemia. However, the molecular mechanism of Acu for treating ischemic stroke has not yet been detailedly elucidated. Based our microarray analysis results, mitochondrial ribosomal protein L41 (MRPL41), which is related to apoptosis, was identified as the target of Acu. MRPL41 expression was increased in middle cerebral artery occlusion/reperfusion (MCAO/R) model and reduced after Acu treatment. Following, MCAO/R model and oxygen and glucose deprivation/reoxygenation (OGD/R) model were established to explore the effect of MRPL41. Knockdown of MRPL41 increased cell viability and ani-apoptotic protein (Bcl-2) expression, and reduced apoptosis intensity and pro-apoptotic protein (Bax and Cleaved caspase-3) of OGD/R neurons. In vivo, MRPL41 silencing decreased neurological severity score, shrank infarct area, reduced encephaledema and neuron apoptosis. In addition, reduction of MRPL41 caused loss of p53. Our data uncover that Acu targets MRPL41, following with inhibiting neuron apoptosis via p53 pathway, thereby ameliorating ischemic stroke.

摘要

神经元死亡是缺血性中风的关键原因。针灸(Acu)是治疗和改善脑缺血的公认方法。然而,Acu 治疗缺血性中风的分子机制尚未详细阐明。基于我们的微阵列分析结果,与细胞凋亡有关的线粒体核糖体蛋白 L41(MRPL41)被确定为 Acu 的靶点。在大脑中动脉闭塞/再灌注(MCAO/R)模型中,MRPL41 的表达增加,而在 Acu 治疗后则减少。随后,建立了 MCAO/R 模型和氧葡萄糖剥夺/再氧合(OGD/R)模型,以探讨 MRPL41 的作用。MRPL41 的敲低增加了 OGD/R 神经元的细胞活力和抗凋亡蛋白(Bcl-2)的表达,减少了细胞凋亡强度和促凋亡蛋白(Bax 和 Cleaved caspase-3)的表达。在体内,MRPL41 的沉默降低了神经严重程度评分,缩小了梗死面积,减少了脑水肿和神经元凋亡。此外,MRPL41 的减少导致 p53 的丢失。我们的数据揭示了 Acu 靶向 MRPL41,通过 p53 途径抑制神经元凋亡,从而改善缺血性中风。

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