Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan, 619-953, Republic of Korea,
Arch Pharm Res. 2013 Oct;36(10):1252-61. doi: 10.1007/s12272-013-0164-9. Epub 2013 Jun 1.
Intestinal injury is a major cause of death after high-dose radiation exposure. The use of granulocyte-colony stimulating factor (G-CSF) to treat radiation injury has focused on enhancing recovery from hematopoietic radiation syndrome. We evaluated G-CSF for its ability to protect against radiation-induced intestinal injury in rat intestinal epithelial cells (IEC-6) and BALB/c mouse models. For in vitro tests, pre-radiation addition of G-CSF to IEC-6 prevented cytotoxicity and the loss of cell viability. Pre-radiation G-CSF treatment also reduced radiation-induced cleavage of caspase-3 and p53 in IEC-6. For in vivo tests, examination 12 h after abdominal irradiation showed that G-CSF-treated mice were protected against apoptosis of the jejunal crypts. G-CSF-treated mice also showed attenuated intestinal morphological changes 3.5 days after abdominal radiation (10 Gy). G-CSF also reduced the levels of proinflammatory cytokines interleukin-6 and tumor necrosis factor-α after radiation. This study showed that G-CSF may protect against radiation-induced intestinal damage through its anti-apoptotic and anti-inflammatory effects. These results suggest that G-CSF is promising candidate for protection against intestinal mucosal injury following irradiation.
肠损伤是大剂量辐射暴露后死亡的主要原因。使用粒细胞集落刺激因子（G-CSF）治疗辐射损伤的重点是增强造血辐射综合征的恢复。我们评估了 G-CSF 对大鼠肠上皮细胞（IEC-6）和 BALB/c 小鼠模型辐射诱导肠损伤的保护作用。在体外试验中，IEC-6 细胞在辐射前加入 G-CSF 可防止细胞毒性和细胞活力丧失。辐射前 G-CSF 处理还减少了 IEC-6 中 caspase-3 和 p53 的辐射诱导裂解。在体内试验中，腹部照射 12 小时后检查发现，G-CSF 处理的小鼠可防止空肠隐窝的细胞凋亡。接受腹部照射（10 Gy）后 3.5 天，G-CSF 处理的小鼠还显示出肠道形态学变化减弱。G-CSF 还降低了辐射后促炎细胞因子白细胞介素-6 和肿瘤坏死因子-α的水平。本研究表明，G-CSF 可能通过其抗凋亡和抗炎作用来保护肠道免受辐射损伤。这些结果表明，G-CSF 是预防照射后肠黏膜损伤的有前途的候选药物。
