Jaenke R S, Robbins M E, Bywaters T, Whitehouse E, Rezvani M, Hopewell J W
Department of Pathology, Colorado State University, Fort Collins.
Lab Invest. 1993 Apr;68(4):396-405.
Therapeutic abdominal irradiation may be accompanied by late occurring progressive renal disease associated with glomerular mesangial sclerosis and tubular degeneration. Pathogenesis of this lesion is disputed.
Kidneys of mature pigs were irradiated with a single dose of 9.8 Gy 60Co gamma-rays; serial individual kidney glomerular filtration rate and renal biopsies were obtained at 3-4-week intervals with death 24 weeks after irradiation.
Irradiated pigs displayed a progressive reduction in glomerular filtration rate with minimal values observed 12 weeks postirradiation. Morphologic changes in irradiated glomeruli were characterized by leukocytic attachment to capillary endothelial cells 3-6 weeks after irradiation followed by activation and swelling of endothelial cells and occasional microthrombi formation. Similar changes were noted focally in peritubular capillaries with accompanying tubular degeneration and atrophy. In glomeruli these endothelial cell changes were followed by increased capillary permeability and fluid, erythrocyte, platelet, and leukocytic exudation into the subendothelial/mesangial space resulting in compression of glomerular capillary lumina. By 12 weeks postirradiation mesangial cells showed evidence of activation and proliferation accompanied by progressive mesangial expansion and sclerosis with continued reduction of glomerular filtration rate.
It is concluded that endothelial cell injury represents the primary site of radiation damage in the kidney and that the progressive glomerular mesangial sclerosis and reduced renal function of radiation nephropathy may be associated with exposure of capillary elements to various vasoactive and growth promoting factors that stimulate mesangial contraction and proliferation resulting in reduced glomerular filtration area and glomerular filtration rate.
腹部治疗性照射可能会伴随晚期发生的进行性肾脏疾病，该疾病与肾小球系膜硬化和肾小管变性有关。这种病变的发病机制存在争议。
用单剂量9.8 Gy的60Coγ射线照射成年猪的肾脏；每隔3 - 4周获取连续的个体肾脏肾小球滤过率并进行肾活检，照射后24周处死动物。
受照射猪的肾小球滤过率逐渐降低，照射后12周出现最小值。照射后肾小球的形态学变化特征为：照射后3 - 6周白细胞附着于毛细血管内皮细胞，随后内皮细胞活化、肿胀，并偶尔形成微血栓。在肾小管周围毛细血管局部也观察到类似变化，同时伴有肾小管变性和萎缩。在肾小球中，这些内皮细胞变化之后是毛细血管通透性增加，液体、红细胞、血小板和白细胞渗入内皮下/系膜间隙，导致肾小球毛细血管腔受压。照射后12周，系膜细胞显示出活化和增殖的迹象，伴有系膜逐渐扩张和硬化，同时肾小球滤过率持续降低。
得出的结论是，内皮细胞损伤是肾脏辐射损伤的主要部位，放射性肾病中进行性肾小球系膜硬化和肾功能降低可能与毛细血管成分暴露于各种血管活性和生长促进因子有关，这些因子刺激系膜收缩和增殖，导致肾小球滤过面积和肾小球滤过率降低。
