Ischemic stroke is a life-threatening cerebrovascular thrombotic disease, oxidative stress is considered to be a critical factor to stroke pathophysiology. This study aimed to investigate the underlying molecular mechanism and propose the potential therapeutic strategy for ischemic stroke. Bioinformatics analysis based on a public microarray profile (GSE 61616) of ischemic stroke rats was performed as a pilot research. Oxidative stress was enriched as a significantly gene ontology item, and thioredoxin-interacting protein (TXNIP) and MAPK signaling were identified as the hub gene and pathway, respectively. The experiments in middle cerebral artery occlusion rats demonstrated that ischemia induced the activation of oxidative stress. The expressions of TXNIP, p-p38, p-JNK, p-ERK were significantly increased while Nrf2 and HO-1 expressions were decreased after stroke. Rescue assays were conducted in primary cultured neurons to explore the accurate interrelations among these factors. The results indicated that MAPK specific inhibitor and siRNA-TXNIP significantly alleviated the oxidative stress injury induced by oxygen-glucose deprivation. In addition, knocking down of TXNIP inhibited the activation of MAPK pathway and promoted Nrf2 pathway. Taken together, these findings indicated that TXNIP aggravated the oxidative stress injury by regulating MAPK-Nrf2 axis in ischemic stroke. Silencing of TXNIP seems a promising therapeutic strategy to alleviate ischemic stroke.

中文翻译：

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沉默TXNIP可通过调节缺血性卒中中的MAPK-Nrf2轴减轻氧化应激损伤。

缺血性中风是威胁生命的脑血管血栓性疾病，氧化应激被认为是中风病理生理学的关键因素。这项研究旨在调查潜在的分子机制，并提出缺血性中风的潜在治疗策略。作为一项初步研究，进行了基于缺血性中风大鼠的公共微阵列图谱（GSE 61616）的生物信息学分析。氧化应激被丰富作为重要的基因本体论项，硫氧还蛋白相互作用蛋白（TXNIP）和MAPK信号传导分别被确定为中枢基因和途径。在大脑中动脉闭塞大鼠中进行的实验表明，缺血诱导了氧化应激的激活。TXNIP，p-p38，p-JNK，脑卒中后p-ERK显着升高，而Nrf2和HO-1表达降低。在原代培养的神经元中进行了拯救试验，以探索这些因素之间的准确相互关系。结果表明，MAPK特异性抑制剂和siRNA-TXNIP显着减轻了氧葡萄糖剥夺引起的氧化应激损伤。另外，敲低TXNIP抑制了MAPK途径的激活并促进了Nrf2途径。综上所述，这些发现表明TXNIP通过调节缺血性卒中中的MAPK-Nrf2轴而加剧了氧化应激损伤。沉默TXNIP似乎是缓解缺血性卒中的一种有前途的治疗策略。结果表明，MAPK特异性抑制剂和siRNA-TXNIP显着减轻了氧葡萄糖剥夺引起的氧化应激损伤。另外，敲低TXNIP抑制了MAPK途径的激活并促进了Nrf2途径。综上所述，这些发现表明TXNIP通过调节缺血性卒中中的MAPK-Nrf2轴而加剧了氧化应激损伤。沉默TXNIP似乎是缓解缺血性卒中的一种有前途的治疗策略。结果表明，MAPK特异性抑制剂和siRNA-TXNIP显着减轻了氧葡萄糖剥夺引起的氧化应激损伤。另外，敲低TXNIP抑制了MAPK途径的激活并促进了Nrf2途径。综上所述，这些发现表明TXNIP通过调节缺血性卒中中的MAPK-Nrf2轴而加剧了氧化应激损伤。沉默TXNIP似乎是缓解缺血性卒中的一种有前途的治疗策略。这些发现表明，TXNIP通过调节缺血性卒中中的MAPK-Nrf2轴而加剧了氧化应激损伤。沉默TXNIP似乎是缓解缺血性卒中的一种有前途的治疗策略。这些发现表明，TXNIP通过调节缺血性卒中中的MAPK-Nrf2轴而加重了氧化应激损伤。沉默TXNIP似乎是缓解缺血性卒中的一种有前途的治疗策略。