特里普托利德通过诱导小鼠丸精子细胞的线粒体通路中的亡来引起精子发生障碍
Jiantao Zhao1, Maosheng Cao2, Haisheng Yi1
1Department of Andrology, The First Hospital of Jilin University, Jilin University, Changchun 130021, China.
Toxics
|January 8, 2025
概括
特里普托利德通过诱导氧化应激和亡,在小鼠中引起严重的丸损伤和生殖毒性. N-乙-L-氨酸 (NAC) 治疗减轻了这些不良反应,这表明了潜在的治疗策略.
科学领域:
- 生殖毒理学 生殖毒理学
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 来自Tripterygium wilfordii的托利德 (TP) 具有抗瘤特性,但受到严重生殖毒性的限制.
- 了解TP诱导的丸损伤的分子机制对于减轻其临床风险至关重要.
研究的目的:
- 在雄性小鼠中研究三胺诱导的丸损伤背后的机制.
- 为了评估N-乙-L-氨酸 (NAC) 对三类的生殖毒性的保护作用.
主要方法:
- 在C57BL/6J雄性小鼠中建立丸损伤模型,使用三类药物给药.
- 丸组织的转录组测序以确定差异表达的基因和途径.
- 道测定和西部斑点分析以评估细胞亡和线粒体功能.
- 使用GC2细胞系进行体外研究.
主要成果:
- 三类药物治疗导致严重的丸损伤,其特征是亡,改变了线粒体形态,并破坏了细胞循环和分化途径.
- 转录组分析显示了p53信号传递和谷甲代谢途径的丰富.
- 托因增加亲氧化因子和降低抗氧化防御而引起显著的氧化应激.
- N-乙-L-氨酸 (NAC) 的使用有效地减少了丸损伤和亡,减轻了氧化应激.
结论:
- 特里普托利德主要通过氧化应激和线粒体亡诱导男性生殖毒性.
- N-乙-L-氨酸 (NAC) 显示出对三类诱导的丸损伤的保护作用.
- 这项研究为开发策略提供了基础,以管理三类对男性生殖系统的不良影响.
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