Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Ave, Bethesda, MD 20889-5603, USA.
Radiat Res. 2012 Feb;177(2):133-45. doi: 10.1667/rr2627.1. Epub 2011 Oct 20.
The purpose of this study was to elucidate the role of α-tocopherol succinate (α-TS) in protecting mice from gastrointestinal syndrome induced by total-body irradiation. CD2F1 mice were injected subcutaneously with 400 mg/kg of α-TS and exposed to different doses of (60)Co γ radiation, and 30-day survival was monitored. Jejunum sections were analyzed for crypts and villi, PUMA (p53 upregulated modulator of apoptosis), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling - TUNEL). The crypt regeneration in irradiated mice was evaluated by 5-bromo-2-deoxyuridine (BrdU). Bacterial translocation from gut to heart, spleen and liver in α-TS-treated and irradiated mice was evaluated by bacterial culture on sheep blood agar, colistin-nalidixic acid, and xylose-lysine-desoxycholate medium. Our results demonstrate that α-TS enhanced survival in a significant number of mice irradiated with 9.5, 10, 11 and 11.5 Gy (60)Co γ radiation when administered 24 h before radiation exposure. α-TS also protected the intestinal tissue of irradiated mice in terms of crypt and villus number, villus length and mitotic figures. TS treatment decreased the number of TUNEL- and PUMA-positive cells and increased the number of BrdU-positive cells in jejunum compared to vehicle-treated mice. Further, α-TS inhibited gut bacterial translocation to the heart, spleen and liver in irradiated mice. Our data suggest that α-TS protects mice from radiation-induced gastrointestinal damage by inhibiting apoptosis, promoting regeneration of crypt cells, and inhibiting translocation of gut bacteria.
本研究旨在阐明α-生育酚琥珀酸酯（α-TS）在保护小鼠免受全身辐射诱导的胃肠道综合征中的作用。CD2F1 小鼠皮下注射 400mg/kg 的 α-TS，并接受不同剂量（60）Co γ 辐射，监测 30 天的存活率。分析空肠切片的隐窝和绒毛、PUMA（p53 上调凋亡调节剂）和凋亡（末端脱氧核苷酸转移酶 dUTP 缺口末端标记 - TUNEL）。通过 5-溴-2-脱氧尿苷（BrdU）评估照射小鼠中隐窝的再生。通过绵羊血琼脂、黏菌素-萘啶酸和木糖-赖氨酸-去氧胆酸盐培养基上的细菌培养评估 α-TS 处理和照射小鼠的肠道细菌易位到心脏、脾脏和肝脏。我们的结果表明，α-TS 增强了在接受 9.5、10、11 和 11.5Gy（60）Co γ 辐射照射前 24 小时给予的大量接受照射的小鼠的存活率。α-TS 还保护了照射小鼠的肠组织，在隐窝和绒毛数量、绒毛长度和有丝分裂数方面。与 vehicle 处理的小鼠相比，TS 处理降低了空肠中 TUNEL 和 PUMA 阳性细胞的数量，增加了 BrdU 阳性细胞的数量。此外，α-TS 抑制了照射小鼠肠道细菌向心脏、脾脏和肝脏的易位。我们的数据表明，α-TS 通过抑制细胞凋亡、促进隐窝细胞再生和抑制肠道细菌易位来保护小鼠免受辐射诱导的胃肠道损伤。
