人类支气管上皮细胞的细胞和转录反应对体外Delta-9-Tetrahydrocannabinol的细胞和转录反应
Megan S Doldron1, Sourav Chakraborty2, Santosh Anand2
1Department of Biology, University of North Carolina Greensboro, Greensboro, NC 27412, USA.
International journal of molecular sciences
|June 13, 2025
概括
暴露于德尔塔-9-四化甘醇 (THC) 会损害支气管细胞,通过铁死导致死亡. 抑制这种途径保护细胞,揭示了大麻相关呼吸系统损伤的关键机制.
科学领域:
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 德尔塔-9-四大麻 (THC) 是大麻中主要的精神活性化合物.
- 大麻中THC度的增加引发了健康问题,特别是呼吸系统问题.
- 由于THC诱导的支气管上皮细胞死亡的精确分子机制尚未完全理解.
研究的目的:
- 为了研究底层的分子机制的Delta-9-tetrahydrocannabinol (THC) 诱导的支气管上皮细胞死亡.
- 检查各种THC度对细胞活力,氧化应激和人类支气管上皮细胞基因表达的影响.
- 确定涉及THC毒性的关键信号通路.
主要方法:
- 暴露的人类支气管上皮细胞 (BEAS-2B) 在体外不同度的Delta-9-THC (0-1500 ng/mL).
- 评估了细胞活力,氧化应激和脂质过氧化.
- 进行了转录组分析和英才途径分析 (IPA) 以确定受影响的途径.
主要成果:
- 暴露于THC导致支气管上皮细胞活力的剂量依赖性下降.
- 转录组分析显示HIF-1,ferroptosis,AMPK和免疫性通路的激活.
- 铁亡途径的抑制改善了THC诱导的细胞死亡,而激动剂加剧了它.
结论:
- 暴露于德尔塔-9-THC会诱导支气管上皮细胞死亡,可能通过铁亡途径.
- 了解这些机制对于解决与大麻使用相关的呼吸系统健康风险至关重要.
- 向铁亡途径可能提供针对THC诱导的肺损伤的治疗策略.
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