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氨磷汀通过作用于线粒体来刺激骨髓生长和调节细胞因子。

Amifostine acts upon mitochondria to stimulate growth of bone marrow and regulate cytokines.

机构信息

Department of Radiation Oncology, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.

Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, Gainesville, FL, USA.

出版信息

Adv Exp Med Biol. 2013;789:195-201. doi: 10.1007/978-1-4614-7411-1_27.

Abstract

Amifostine is a first-line cytoprotective drug used to prevent radiotherapy-induced or chemotherapy-induced injuries. However, its mechanism of action is not well understood. In this study, freshly harvested bone marrow cells were treated with amifostine and analyzed with a series of mitochondrial indices. In vitro results showed that bone marrow cells treated with amifostine 0.5 h before irradiation (0.5 Gy) experienced several benefits, as compared to vehicle controls, including (1) reduced reactive oxygen species levels, which reduced the production of free radicals; (2) better preservation of mitochondria, as indicated by MitoTracker-positive staining and the increased intensity of staining; (3) reduced apoptosis, as demonstrated by Annexin V staining; and (4) a better proliferation rate, as illustrated by MTT assay. Our in vitro studies showed that amifostine-treated mice exhibited (1) higher ATP production; (2) reduced plasma IL-2 levels, suppressing the immune response triggered by radiotoxicity; and (3) enhanced radiation-induced production of granulocyte colony-stimulating factor. All of these processes benefit recovery from radiation-induced damage.

摘要

氨磷汀是一种用于预防放疗或化疗引起的损伤的一线细胞保护药物。然而,其作用机制尚不清楚。在这项研究中,我们用氨磷汀处理新鲜收获的骨髓细胞,并分析了一系列线粒体指标。体外实验结果表明,与对照组相比,在照射(0.5Gy)前 0.5 小时用氨磷汀处理的骨髓细胞具有以下几个优势:(1)减少活性氧水平,从而减少自由基的产生;(2)线粒体得到更好的保护,表现为 MitoTracker 阳性染色和染色强度增加;(3)凋亡减少,表现为 Annexin V 染色;(4)增殖率更高,MTT 检测表明。我们的体外研究表明,氨磷汀处理的小鼠表现出(1)更高的 ATP 产量;(2)降低血浆中 IL-2 水平,抑制由放射毒性引发的免疫反应;(3)增强辐射诱导的粒细胞集落刺激因子的产生。所有这些过程都有利于从辐射引起的损伤中恢复。

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