Genistein protects against biomarkers of delayed lung sequelae in mice surviving high-dose total body irradiation
Genistein protects against biomarkers of delayed lung sequelae in mice surviving high-dose total body irradiation
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DOI：
10.1269/jrr.07121
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发表时间：
2008-07-01
影响因子：
2
通讯作者：
Landauer, Michael R.
中科院分区：
文献类型：
--
作者：
Day, Regina M.;Barshishat-Kupper, Michal;Landauer, Michael R.
全身照射/肺纤维化/金雀异黄素/放射防护/微核/肺炎。在 C57BL/6J 雌性小鼠中检查金雀异黄素对 30 天生存和迟发性肺损伤的影响。在全身照射（7.75 Gy Co-60.0.6 Gy/min）前 24 小时，进行单次皮下注射载体（PEG-400）或金雀异黄酮（200 mg/kg）。实验组为：无治疗+假手术(NC)、载体+假手术(VC)、金雀异黄素+假手术(GC)、仅辐射(NR)、载体+辐射(VR)、金雀异黄素+辐射(GR)。 7.75 Gy 后 30 天的存活率为：NR 23%、VR 53% 和 GR 92%，表明金雀异黄素对急性辐射损伤有显着的保护作用。金雀异黄素还可以减轻辐射后第 13-28 天由辐射引起的体重减轻。辐射后 24 小时对第一代肺成纤维细胞进行微核分析。与 NR 小鼠相比，GR 处理小鼠肺部成纤维细胞的微核显着减少。通过组织化学染色检查胶原沉积。照射后 90 天，一半未经处理和媒介物照射的小鼠肺部出现富含胶原蛋白的小斑块，而所有金雀异黄素处理的小鼠的肺部形态正常。辐射后 90 天，辐射降低了 COX-2、转化生长因子受体 (TGF beta R) I 和 II 的表达。金雀异黄素可阻止 TGF β RI 的减少。然而，到照射后 180 天时，所有组中的这些蛋白质都恢复正常。这些结果表明，金雀异黄素可以防止雌性小鼠急性辐射引起的死亡，并且与 NR 或 VR 相比，GR 治疗的小鼠 C 减少了肺损伤。这些数据表明金雀异黄素可以预防一系列辐射损伤。
Total body irradiation/Lung fibrosis/Genistein/Radioprotection/Micronuclei/Pneumonitis.The effects of genistein on 30-day survival and delayed lung injury were examined in C57BL/6J female mice. A single subcutaneous injection of vehicle (PEG-400) or genistein (200 mg/kg) was administered 24 h before total body irradiation (7.75 Gy Co-60. 0.6 Gy/min). Experimental groups were: No treatment + Sham (NC), Vehicle + Sham (VC), Genistein + Sham (GC), Radiation only (NR), Vehicle + Radiation (VR), Genistein + Radiation (GR). Thirty-day survivals after 7.75 Gy were: NR 23%, VR 53% and GR 92%, indicating significant protection from acute radiation injury by genistein. Genistein also mitigated radiation-induced weight loss on days 13-28 postirradiation. First generation lung fibroblasts were analyzed for micronuclei 24 h postirradiation. Fibroblasts from the lungs of GR-treated mice had significantly reduced micronuclei compared with NR mice. Collagen deposition was examined by histochemical staining. At 90 days postirradiation one half of the untreated and vehicle irradiated mice had focal distributions of small collagen-rich plaques in the lungs, whereas all of the genistein-treated animals had morphologically normal lungs. Radiation reduced the expression of COX-2, transforming growth factor-receptor (TGF beta R) I and II at 90 days after irradiation. Genistein prevented the reduction in TGF beta RI. However, by 180 days postirradiation, these proteins normalized in all groups. These results demonstrate that genistein protects against acute radiation-induced mortality in female mice and that GR-treated mice have C reduced lung damage compared to NR or VR. These data suggest that genistein is protective against a range of radiation injuries.