Department of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Saitama, Japan.
J Radiat Res. 2010;51(2):145-56. doi: 10.1269/jrr.09078. Epub 2009 Dec 4.
While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome.
虽然骨髓或干细胞移植可以挽救意外暴露于致死剂量辐射的患者的骨髓再生障碍，但辐射引起的不可逆胃肠道损伤（GI 综合征）是致命的。我们研究了抗坏血酸对小鼠辐射诱导的 GI 综合征的影响。抗坏血酸（150mg/kg/天）口服给予小鼠 3 天，然后对其进行全身照射（WBI）。照射后 24 小时进行骨髓移植（BMT）可挽救接受小于 12Gy WBI 的小鼠。没有接受 14Gy-WBI 的小鼠存活下来，因为辐射引起的 GI 综合征，即使它们接受了 BMT。然而，抗坏血酸预处理显著抑制了隐窝细胞中的辐射诱导的 DNA 损伤，并防止了肠黏膜的脱落；因此，抗坏血酸联合 BMT 可挽救 14Gy-WBI 后的小鼠。DNA 微阵列分析表明，照射在上皮细胞中上调了与细胞凋亡相关的基因的表达，包括与半胱氨酸蛋白酶-9 介导的内在途径以及半胱氨酸蛋白酶-8 介导的外在途径相关的基因，并且在抗坏血酸预处理的小鼠中下调了这些基因的表达。因此，抗坏血酸预处理可能有效预防辐射诱导的 GI 综合征。
