内皮细胞亡作为主要的损伤,在小鼠中启动肠道辐射损伤
1Laboratory of Signal Transduction and, Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Science (New York, N.Y.)
|July 14, 2001
概括
放射治疗通过诱导微血管内皮细胞亡,从而损害干细胞功能,导致胃肠道 (GI) 损伤. 抑制这种内皮损伤保护小鼠免受致命的胃肠道综合征,提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 辐射生物学 辐射生物学
- 胃肠病学 胃肠病学
背景情况:
- 化疗和放射治疗可能会导致胃肠道 (GI) 损伤,限制它们在癌症治疗中的有效性.
- 放射引起的胃肠道损伤被认为源于Lieberkühn.crypt中的上皮干细胞受损.
研究的目的:
- 为了研究辐射诱导的胃肠道损伤的主要细胞点.
- 确定潜在的治疗点,以减轻辐射诱导的胃肠道综合征.
主要方法:
- 利用小鼠模型研究辐射对胃肠道的影响.
- 使用基本纤维细胞生长因子 (bFGF) 进行内皮细胞亡的药理抑制.
- 研究了酸性基因酶基因的遗传删除,以评估其在辐射保护中的作用.
主要成果:
- 微血管内皮细胞亡被确定为辐射暴露后干细胞功能障碍的主要原因.
- 抑制内皮细胞亡,无论是药理上使用bFGF还是基因上,都能防止辐射诱导的密室损伤,器官衰竭和死亡.
- 在内皮细胞中发现了FGF受体转录,但在密室细胞中没有发现,这表明内皮损伤先于密室干细胞损伤.
结论:
- 辐射诱导的微血管内皮细胞亡是导致GI综合征的关键初始事件.
- 向内皮细胞亡是一种有希望的策略,可以预防或减少辐射引起的肠损伤.
- 这项研究为在癌症治疗期间保护肠道的新型治疗干预措施开辟了道路.
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