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用RISPERIDONE进行的短期治疗改善了1,2-二甲基诱导的肝功能障碍
Hai Duc Nguyen1, Won Hee Jo1, Ngoc Hong Minh Hoang1
1Department of Pharmacy, College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea.
International immunopharmacology
|July 27, 2023
概括
这项研究表明,RISPERIDONE可以保护小鼠免受1,2-二甲基 (DAB) 诱导的肝损伤. 里斯佩里治疗减少了肝损伤标志物和炎症反应,这表明它对DAB诱导的肝毒性有治疗潜力.
科学领域:
- 毒理学 毒理学 毒理学
- 药理学 药理学是指药理学的学科.
- 肝病学 肝病学是一种肝病学.
背景情况:
- 已知1,2-二甲基 (DAB) 影响中枢神经系统,但对肝脏的影响仍未得到充分研究.
- 抗精神病药物里斯佩里已经显示出对DAB的神经保护作用,但其肝脏保护潜力尚不清楚.
研究的目的:
- 在小鼠模型中研究RISPERIDONE对DAB诱导的肝功能障碍的肝保护作用.
- 阐明DAB诱导的肝损伤和RISPERIDONE的保护作用背后的分子机制.
主要方法:
- 雄性C57BL/6小鼠接受了DAB (5 mg/kg) 治疗1周,随后接受了RISPERIDONE (0.125-0.25 mg/kg) 治疗2周.
- 分析了肝功能生物标记物,氧化应激标记物,炎症性细胞因子,与亡相关的蛋白质和关键信号通路 (TLR4 / JNK / NF-κB,Jak2 / Stat通路,IRS1 / PI3K / AKT / MDM2).
- 进行了in silico分析,以确定涉及DAB诱导的肝损伤和RISPERIDONE作用的分子标和途径.
主要成果:
- DAB暴露增加了肝损伤生物标志物,氧化应激,炎症和亡,同时改变了特定的信号通路.
- 里斯佩里治疗,特别是高剂量治疗,显著减轻了DAB诱导的肝损伤,并使受影响的生物标志物和途径正常化.
- 在分析中确定了Stat3,Caspase-3,AKT,IL-1β,miR-26b-5p,miR-34a-5p,NFKB1和NFKB2作为关键的分子参与者和涉及的"AGE-RAGE信号通路"和"酒精性肝病"等途径.
结论:
- 里斯佩里对DAB诱导的肝功能障碍有显著的肝保护作用.
- 这些研究结果表明,RISPERIDONE可以通过调节氧化应激,炎症,亡和关键细胞信号通路来减轻DAB诱导的肝损伤.
- 这项研究强调了瑞斯佩里在治疗DAB暴露引起的肝损伤方面的治疗潜力.
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