Abstract：
Sericin (Ser) is a natural neuroactive macromolecule with diverse pharmacological properties, and our previous findings have shown its neuroprotective potentials. This study aimed to investigate the therapeutic potential of Ser on cognitive dysfunction induced by transient global cerebral ischemia/reperfusion (tGI/R) and its mechanism of action. The tGI/R was induced in BALB/c mice by bilateral occlusion of the common carotid arteries for two 5 min followed by a 10-min reperfusion period. After 24 h, mice were treated with normal saline or different doses of Ser (100, 200, and 300 mg/kg) for 10 days. Cognitive performances were assessed using the Barnes maze and social interaction tasks. Oxidative stress markers including superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant capacity (TAC), and malondialdehyde (MDA) as well as pro-inflammatory cytokines (interleukin (IL)-6 and tumor necrosis factor-alpha) and anti-inflammatory cytokine (IL-10) were assessed in the hippocampus. Markers of apoptosis (pro- and cleaved caspase-9 and 3, Bax, and Bcl-2) were assessed by Western blotting. Besides, transferase-mediated dUTP nick end-labeling assay was used to detect apoptotic cell death. We show here that Ser administration improved tGI/R-induced cognitive deficits, enhanced the activity of SOD and GPx, increased TAC levels, while reduced MDA levels. Notably, Ser decreased neuronal apoptotic cell death in the hippocampal dentate gyrus (DG) region, accompanied by suppression of neuroinflammation, downregulation of pro-apoptotic proteins (caspase-9, caspases-3, and Bax), and upregulation of anti-apoptotic protein, Bcl-2. Taken together, Ser administration protected hippocampal neurons from apoptotic cell death by impeding oxidative stress and inflammatory responses and, in turn, improved cognitive function in the tGI/R mice.
摘要：
丝胶（Ser）是一种天然的神经活性大分子，具有多种药理特性，我们之前的发现已经显示了它的神经保护潜力。本研究旨在探讨Ser对短暂性全脑缺血/再灌注(tGI/R)所致认知功能障碍的治疗潜力及其作用机制。通过双侧颈总动脉闭塞两个5分钟，然后再灌注10分钟，在BALB/c小鼠中诱导tGI/R。24小时后，小鼠用生理盐水或不同剂量的Ser(100、200和300mg/kg)处理10天。使用Barnes迷宫和社交互动任务评估认知表现。氧化应激标志物，包括超氧化物歧化酶（SOD），谷胱甘肽过氧化物酶（GPx），总抗氧化能力(TAC)，在海马中评估丙二醛（MDA）以及促炎细胞因子（白介素（IL）-6和肿瘤坏死因子-α）和抗炎细胞因子（IL-10）。凋亡标志物（pro-和裂解的caspase-9和3，Bax，和Bcl-2）通过蛋白质印迹法评估。此外,转移酶介导的dUTP缺口末端标记测定法用于检测凋亡细胞死亡。我们在这里表明，Ser管理改善了tGI/R诱导的认知缺陷，增强了SOD和GPx的活性，增加的TAC水平，同时降低MDA水平。值得注意的是,Ser减少了海马齿状回（DG）区的神经元凋亡细胞死亡，伴随着神经炎症的抑制，下调促凋亡蛋白（caspase-9，caspases-3和Bax），和上调抗凋亡蛋白，Bcl-2.一起来看,Ser给药通过阻止氧化应激和炎症反应保护海马神经元免于凋亡细胞死亡，反过来,改善tGI/R小鼠的认知功能。
