Geraci J P, Mariano M S, Jackson K L
Department of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle 98195.
Radiat Res. 1992 Mar;129(3):322-32.
Prior to whole-liver irradiation (0, 15, 25 Gy) rats were not treated, placed on a protein-deficient diet for 2 weeks, administered cyclophosphamide, and/or depleted of intracellular glutathione by injection with buthionine sulfoximide and diethyl maleate. At various times (0 to 84 days) after 0- and 25-Gy liver irradiation, liver function, liver mass, and hydroxyproline content were measured in nontreated animals. Liver function was measured in all other preirradiation regimens 2 to 3 months postirradiation. Histology and/or India ink perfusion of the liver were done on ascitic and jaundiced animals from all treatment groups. Approximately 20% of the 25-Gy whole-liver-irradiated animals in each preirradiation treatment group developed clinical signs of acute hepatitis (ascites, jaundice, and elevated liver enzymes in the plasma) 70 to 100 days after irradiation. Twenty-five-gray whole-liver irradiation also resulted in significant liver fibrosis that preceded the onset of liver dysfunction. Fibrotic changes were most dramatic in and around hepatic veins, sometimes resulting in complete or partial occlusion that disrupted intrahepatic blood flow and diminished liver function. In addition, a substantial accumulation of fluid in the liver of 25-Gy-irradiated livers occurred, resulting in a lower dry/wet liver weight ratio. Functional hepatic injury was enhanced by preirradiation treatment with a protein-deficient diet, cyclophosphamide, and/or depletion of intracellular glutathione. This enhancement of functional injury was pronounced after 15-Gy whole-liver irradiation when injury from radiation alone was minimal.
在进行全肝照射（0、15、25 Gy）之前，对大鼠不进行处理，或使其接受为期2周的蛋白质缺乏饮食，或给予环磷酰胺，和/或通过注射丁硫氨酸亚砜胺和马来酸二乙酯消耗细胞内谷胱甘肽。在0 Gy和25 Gy肝脏照射后的不同时间（0至84天），对未处理的动物测量肝功能、肝脏质量和羟脯氨酸含量。在所有其他照射前方案照射后2至3个月测量肝功能。对所有治疗组出现腹水和黄疸的动物进行肝脏组织学检查和/或印度墨汁灌注。在每个照射前治疗组中，约20%接受25 Gy全肝照射的动物在照射后70至100天出现急性肝炎的临床症状（腹水、黄疸和血浆肝酶升高）。25 Gy全肝照射还导致在肝功能障碍发生之前出现明显的肝纤维化。纤维化变化在肝静脉及其周围最为显著，有时导致完全或部分阻塞，从而破坏肝内血流并降低肝功能。此外，接受25 Gy照射的肝脏中出现大量液体蓄积，导致肝干/湿重比降低。蛋白质缺乏饮食、环磷酰胺和/或细胞内谷胱甘肽消耗的照射前处理会增强功能性肝损伤。当单独辐射造成的损伤很小时，这种功能性损伤的增强在15 Gy全肝照射后尤为明显。
