Molecular mechanisms of irradiation-induced impairment eNOS expression

辐射诱导 eNOS 表达损伤的分子机制

基本信息

批准号：
12670077
负责人：
HATTORI Yuichi
金额：
$ 1.79万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670077/
关键词：
irradiation endothelium-dependent relaxation endothelial nitric oxide synthase free radical scavenger rabbit ear artery Edaravone eNOS 血管内皮細胞

项目摘要

We investigated the therapeutic effect of edaravone, a free radical scavenger, on alterations in endothelium-dependent relaxation and endothelial nitric oxide synthase (eNOS) expression in the rabbit central artery at 2 weeks after exposure to a dose of 45 Gy radiation with a cobalt^<60> unit. For treatment with edaravone, edaravone was given daily to the animals from the day before irradiation at an intrapenetreal dose of 10 mg/kg twice a day. The endothelium-dependent relaxant response to acetylcholine was markedly impaired in irradiated vessels. Edaravone treatment improved the response to the level observed in nonirradiated control vessels. Using immunohistochemical and Western blot techniques, we showed that protein expression of eNOS in irradiated vessels was reduced to about 50% of control and that edaravone treatment restored it nearly to intact levels. Gene expression of eNOS, analyzed by RT-PCR, was found to be reduced from the control level by 47% following irradiation. The reduction in eNOS mRNA observed in irradiated vessels was almost completely prevented by edaravone treatment. These results suggest that edaravone has a protective effect on the reduced expression of eNOS and its associated endothelial cell dysfunction in the vessels following irradiation. We thus assume that oxygen free radicals may be closely related to the irradiation-induced derangement of the eNOS gene regulation.

我们研究了依达拉奉（一种自由基清除剂）对兔子中央动脉暴露于 45 Gy 剂量的钴放射线 2 周后内皮依赖性舒张和内皮一氧化氮合酶 (eNOS) 表达变化的治疗效果。 <60> 单位。对于用依达拉奉治疗，从照射前一天开始每天向动物给予依达拉奉，腹腔内剂量为10mg/kg，每天两次。在受辐射的血管中，内皮依赖性的乙酰胆碱松弛反应明显受损。依达拉奉治疗将反应改善至未照射对照血管中观察到的水平。使用免疫组织化学和蛋白质印迹技术，我们发现受辐射血管中 eNOS 的蛋白表达降低至对照的约 50%，而依达拉奉治疗将其恢复到几乎完整的水平。通过 RT-PCR 分析发现，辐射后 eNOS 的基因表达较对照水平降低了 47%。依达拉奉治疗几乎完全阻止了受辐射血管中观察到的 eNOS mRNA 的减少。这些结果表明，依达拉奉对辐射后血管中 eNOS 表达减少及其相关的内皮细胞功能障碍具有保护作用。因此我们推测氧自由基可能与辐射引起的 eNOS 基因调控紊乱密切相关。