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硫辛酸通过调节创伤性脑损伤后 Nrf2 信号通路抑制氧化应激诱导的细胞凋亡。

Alpha lipoic acid inhibits oxidative stress-induced apoptosis by modulating of Nrf2 signalling pathway after traumatic brain injury.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, China.

Department of Neurosurgery, Huai'an Second People's Hospital, Xuzhou Medical College, Huai'an, Jiangsu Province, China.

出版信息

J Cell Mol Med. 2019 Jun;23(6):4088-4096. doi: 10.1111/jcmm.14296. Epub 2019 Apr 15.

Abstract

Alpha lipoic acid (ALA) is a powerful antioxidant which has been widely used in the treatment of different system diseases, such as cardiovascular and cerebrovascular diseases. But, there are few studies that refer to protective effects and potential mechanisms on traumatic brain injury (TBI). This study was carried out to investigate the neuroprotective effect following TBI and illuminate the underlying mechanism. Weight drop-injured model in rats was induced by weight-drop. ALA was administrated via intraperitoneal injection after TBI. Neurologic scores were examined following several tests. Neurological score was performed to measure behavioural outcomes. Nissl staining and TUNEL were performed to evaluate the neuronal apoptosis. Western blotting was engaged to analyse the protein content of the Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream protein factors, including hemeoxygenase-1 (HO-1) and quinine oxidoreductase-1 (NQO1). ALA treatment alleviated TBI-induced neuron cell apoptosis and improved neurobehavioural function by up-regulation of Nrf2 expression and its downstream protein factors after TBI. This study presents new perspective of the mechanisms responsible for the neuronal apoptosis of ALA, with possible involvement of Nrf2 pathway.

摘要

硫辛酸(ALA)是一种强大的抗氧化剂,已广泛用于治疗心血管和脑血管等多种系统疾病。但是,很少有研究涉及外伤性脑损伤(TBI)的保护作用和潜在机制。本研究旨在探讨 TBI 后的神经保护作用,并阐明其潜在机制。通过落体伤诱导大鼠的落体损伤模型。TBI 后通过腹腔注射给予 ALA。进行多项测试后检查神经评分。神经评分用于测量行为结果。进行尼氏染色和 TUNEL 评估神经元凋亡。Western blot 用于分析核因子红细胞 2 相关因子 2(Nrf2)及其下游蛋白因子的蛋白含量,包括血红素加氧酶-1(HO-1)和醌氧化还原酶-1(NQO1)。ALA 治疗通过上调 TBI 后 Nrf2 表达及其下游蛋白因子,减轻 TBI 诱导的神经元细胞凋亡,改善神经行为功能。这项研究为 ALA 诱导的神经元凋亡的机制提供了新的视角,可能涉及 Nrf2 途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15ef/6533507/761b39c79fe7/JCMM-23-4088-g001.jpg

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