关键词: Apoptosis BMAL1 EGCG Oxidative stress Surgical brain injury

Mesh : Animals Catechin / analogs & derivatives pharmacology ARNTL Transcription Factors / metabolism Male Up-Regulation / drug effects Rats Rats, Sprague-Dawley Oxidative Stress / drug effects Neuroprotective Agents / pharmacology Disease Models, Animal Brain Injuries / metabolism drug therapy Brain Edema / metabolism drug therapy Apoptosis / drug effects Antioxidants / pharmacology

来  源:   DOI:10.1016/j.brainresbull.2024.111033

Abstract:
Brain Muscle ARNT-Like Protein 1 (BMAL1) suppresses oxidative stress in brain injury during surgery. Epigallocatechin-3-gallate (EGCG), a monomer in green tea, has been identified as an antioxidant and a potential agonist for BMAL1. In this work, the mechanism by which BMAL1 is regulated was investigated, as well as the therapeutic effect of EGCG on surgically injured rats. The pathological environment after brain injury during surgery was simulated by excising the right frontal lobe of rats. Rats received an intraperitoneal injection of EGCG immediately after surgery. Neurological scores and cerebral edema were recorded after surgery. Fluoro-Jade C staining, TUNEL staining, western blot, and lipid peroxidation analyses were conducted 3 days later. Here we show that the endogenous BMAL1 level decreased after brain injury. Postoperative administration of EGCG up-regulated the content of BMAL1 around the cerebral cortex, reduced the oxidative stress level, reduced neuronal apoptosis and the number of degenerated neurons, alleviated cerebral edema, and improved neurological scores in rats. This suggests that BMAL1 is an effective target for treating surgical brain injury, as well as that EGCG may be a promising agent for alleviating postoperative brain injury.
摘要:
脑肌ARNT样蛋白1(BMAL1)在手术中抑制脑损伤中的氧化应激。表没食子儿茶素-3-没食子酸酯(EGCG),绿茶中的单体,已被确定为BMAL1的抗氧化剂和潜在激动剂。在这项工作中,研究了BMAL1的调控机制,以及EGCG对手术损伤大鼠的治疗作用。通过切除大鼠右额叶模拟手术中脑损伤后的病理环境。手术后立即将大鼠腹膜内注射EGCG。术后记录神经功能评分和脑水肿。Fluoro-JadeC染色,TUNEL染色,westernblot,3天后进行脂质过氧化分析。在这里,我们显示内源性BMAL1水平在脑损伤后降低。术后给予EGCG上调大脑皮质周围BMAL1的含量,降低氧化应激水平,减少神经元凋亡和退化神经元的数量,减轻脑水肿,和改善大鼠的神经评分。这表明BMAL1是治疗外科脑损伤的有效靶点,以及EGCG可能是减轻术后脑损伤的有前途的药物。
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