通过调节昼夜基因和激活Nrf2通路,Ruscogenin的定时使用可缓解脑缺血-再输液损伤
Sanli Zhang1, Yan Yu1, Mingyue Sheng1
1Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, Jiangsu 211198, China; State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, 639 Longmian Road, Nanjing, Jiangsu 211198, China.
概括
俄罗斯素 (Rus) 给药的时间显著影响其在预防脑缺血-再输液损伤 (IRI) 方面的有效性. 晚上给药 (17:00-19:00) 显示出最好的结果,由Nrf2通路介导.
科学领域:
- 药理学 药理学是指药理学的学科.
- 神经科学是一个神经科学.
- 时间生物学 时间生物学
背景情况:
- 众所周知,Ruscogenin (Rus) 是来自Ophiopogon japonicus的类固醇原蛋白,可以缓解脑缺血-再输液损伤 (IRI).
- 然而,Rus的慢药学效应在很大程度上仍未被探索.
研究的目的:
- 调查Rus定时给药对减轻小鼠实验性大脑IRI的影响.
- 阐明潜在的机制,特别是昼夜钟基因和Nrf2通路的作用.
主要方法:
- 小鼠在3天的时间内在四个不同的时间点接受Rus (10mg/kg),随后进行中脑动脉封闭 (MCAO) 手术.
- 评估包括行为测试,心脏病发作体积测量,qPCR,以及对炎症标志物,氧化应激指标和时钟基因的西方斑点分析.
- 通过使用 Nrf2 阻断剂 (ATRA) 进一步研究了 Nrf2 途径.
主要成果:
- Rus的使用减少了脑梗塞的数量,并改善了行为结果.
- 当Rus在17:00-19:00之间服用时,观察到最佳的治疗效果.
- 这种时间调节上调了关键的昼夜钟基因 (Per1,Bmal1,Clock,Rev-erbα) 和Nrf2通路,包括其下游目标HO-1和NQO1.
- 与Nrf2抑制剂 (ATRA) 联合使用降低了Rus.的保护作用.
结论:
- 在预防大脑IRI方面,Ruscogenin的疗效受到药物服用时间的显著影响.
- Nrf2信号通路在调解俄罗斯的慢性治疗效果方面发挥着至关重要的作用.
- 这些发现强调了慢药学在优化大脑IRI治疗中的重要性.
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