青藤碱是药用植物青藤的主要生物活性成分,具有神经保护作用。本研究旨在评估青藤碱在缓解三甲基锡 (TMT) 诱导的认知功能障碍方面的有益作用。TMT腹腔注射(8 mg/kg,一次),青藤碱每日口服给药TMT 后 1 小时,持续 3 周,剂量为 25 或 100 mg/kg。在各种行为测试中评估认知表现。此外,还测量了氧化应激和炎症相关因素,并对海马进行了组织化学评估。青藤碱剂量为 100 mg/kg 显着和部分增加新物体识别 (NOR) 中的辨别指数,改善短期 Y 迷宫中的交替,增加被动回避范式中的逐步潜伏期,并减少探测试验错误和潜伏期在巴恩斯迷宫任务中。此外,青藤碱在一定程度上阻止了丙二醛 (MDA)、活性氧 (ROS)、蛋白质羰基、亚硝酸盐、超氧化物歧化酶 (SOD)、肿瘤坏死因子 α (TNFα)、白细胞介素 6 (IL 6)、乙酰胆碱酯酶 (AChE) 的不当海马变化。 ) 活动,β 分泌酶 1 (BACE 1) 活性和线粒体膜电位 (MMP) 对谷胱甘肽 (GSH)、过氧化氢酶、谷胱甘肽还原酶、谷胱甘肽过氧化物酶和髓过氧化物酶 (MPO) 没有显着影响。此外,观察到作为星形胶质细胞活性指标的胶质纤维酸性蛋白 (GFAP) 的较低反应性 (IRA) 和青藤碱处理后 CA1 锥体神经元的损失减弱。该研究表明青藤碱可以减轻 TMT 引起的认知功能障碍,这部分是由于其减弱了海马氧化应激和神经炎症。观察到胶质纤维酸性蛋白 (GFAP) 的较低反应性 (IRA) 作为星形胶质细胞活性的指标,并且青藤碱处理后 CA1 锥体神经元的损失减弱。该研究表明青藤碱可以减轻 TMT 引起的认知功能障碍,这部分是由于其减弱了海马氧化应激和神经炎症。观察到胶质纤维酸性蛋白 (GFAP) 的较低反应性 (IRA) 作为星形胶质细胞活性的指标,并且青藤碱处理后 CA1 锥体神经元的损失减弱。该研究表明青藤碱可以减轻 TMT 引起的认知功能障碍,这部分是由于其减弱了海马氧化应激和神经炎症。
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Sinomenine Attenuates Trimethyltin-Induced Cognitive Decline via Targeting Hippocampal Oxidative Stress and Neuroinflammation
Sinomenine is the main bioactive ingredient of the medicinal plant Sinomenium acutum with neuroprotective potential. This study was designed to assess beneficial effect of sinomenine in alleviation of trimethyltin (TMT)-induced cognitive dysfunction. TMT was administered i.p. (8 mg/kg, once) and sinomenine was daily given p.o. 1 h after TMT for 3 weeks at doses of 25 or 100 mg/kg. Cognitive performance was assessed in various behavioral tests. In addition, oxidative stress- and inflammation-associated factors were measured and histochemical evaluation of the hippocampus was conducted. Sinomenine at a dose of 100 mg/kg significantly and partially increased discrimination index in novel object recognition (NOR), improved alternation in short-term Y maze, increased step-through latency in passive avoidance paradigm, and also reduced probe trial errors and latency in the Barnes maze task. Moreover, sinomenine somewhat prevented inappropriate hippocampal changes of malondialdehyde (MDA), reactive oxygen species (ROS), protein carbonyl, nitrite, superoxide dismutase (SOD), tumor necrosis factor α (TNFα), interleukin 6 (IL 6), acetylcholinesterase (AChE) activity, beta secretase 1 (BACE 1) activity, and mitochondrial membrane potential (MMP) with no significant effect on glutathione (GSH), catalase, glutathione reductase, glutathione peroxidase, and myeloperoxidase (MPO). In addition, lower reactivity (IRA) for glial fibrillary acidic protein (GFAP) as an index of astrocyte activity was observed and loss of CA1 pyramidal neurons was attenuated following sinomenine treatment. This study demonstrated that sinomenine could lessen TMT-induced cognitive dysfunction which is partly due to its attenuation of hippocampal oxidative stress and neuroinflammation.