Ischemic brain injury (IBI) is a common acute cerebral vessel disease that occurs secondary to blockage in arteries, mainly characterized by insufficient blood supply to the brain. The transcription factor c-Myc in IBI continues to be implicated in numerous studies. This study was conducted with emphasis placed on the underlying mechanism of c-Myc in IBI. Clinical samples were collected from IBI patients. Middle cerebral artery occlusion (MCAO) was induced in mice by inserting a suture from the external carotid artery to the anterior cerebral artery through the internal carotid artery to mechanically block the blood supply at the origin of the middle cerebral artery, and cortical neurons from mice were exposed to oxygen glucose deprivation (OGD) conditions for IBI model in vitro construction. RT-qPCR was performed to determine microRNA-23b (miR-23b) expression. TUNEL staining and Western blot analysis was conducted to detect apoptosis. The regulatory relationship was analyzed by dual-luciferase reporter gene assay. After loss- and gain-of-function assays, triphenyltetrazolium chloride staining was carried out to detect the area of cerebral infarction, after which the spatial memory in mice was evaluated with Morris water maze test. As per our findings, miR-23b was upregulated in the serum of IBI patients and OGD-treated murine primary neurons. Silencing of miR-23b resulted in reduced OGD-induced neuronal apoptosis. miR-23b inversely targeted nuclear factor erythroid 2-related factor 2 (Nrf2) and c-Myc negatively regulated miR-23b expression. Overexpression of c-Myc and inhibition of miR-23b led to reduced neurological scores of infarction area, neuronal apoptosis, shortened platform arrival time and significantly increased the time spent on the platform quadrant and the times of crossing the platform in vivo. Collectively, downregulated miR-23b by c-Myc might alleviate IBI by upregulating Nrf2.

中文翻译：

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转录因子 c-Myc 下调 miR-23b 通过上调 Nrf2 减轻缺血性脑损伤

缺血性脑损伤（IBI）是一种常见的急性脑血管疾病，继发于动脉阻塞，主要表现为脑部供血不足。IBI 中的转录因子 c-Myc 继续与许多研究有关。本研究的重点是 c-Myc 在 IBI 中的潜在机制。临床样本采集自 IBI 患者。通过将缝线从颈外动脉经颈内动脉插入大脑前动脉，以机械方式阻断大脑中动脉起始部的血液供应，诱导小鼠大脑中动脉闭塞（MCAO），并从小鼠中提取皮质神经元暴露于氧糖剥夺（OGD）条件下构建 IBI模型。进行 RT-qPCR 以确定 microRNA-23b (miR-23b) 的表达。进行TUNEL染色和Western印迹分析来检测细胞凋亡。通过双荧光素酶报告基因分析分析调控关系。功能丧失和获得实验后，进行氯化三苯基四唑染色检测脑梗死面积，然后用Morris水迷宫测试评估小鼠的空间记忆。根据我们的研究结果，IBI 患者和 OGD 治疗的小鼠原代神经元的血清中 miR-23b 上调。miR-23b 的沉默导致 OGD 诱导的神经元凋亡减少。miR-23b 反向靶向核因子红细胞 2 相关因子 2 (Nrf2)，c-Myc 负向调节 miR-23b 表达。c-Myc的过表达和miR-23b的抑制导致梗死区神经学评分降低、神经元凋亡、平台到达时间缩短、在平台象限上花费的时间和体内穿越平台的次数显着增加。总的来说，c-Myc 下调 miR-23b 可能通过上调 Nrf2 来缓解 IBI。