Robbins M E, Jaenke R S, Bywaters T, Golding S J, Rezvani M, Whitehouse E, Hopewell J W
CRC Normal Tissue Radiobiology Research Group, Research Institute (University of Oxford), United Kingdom.
Radiat Res. 1993 Sep;135(3):351-64.
Both kidneys of 12 mature female pigs received either a single dose of 9.8 Gy 60Co gamma rays or sham irradiation. At intervals of 1-4 weeks serial renal biopsies were obtained, followed by sacrifice at 24 weeks after irradiation. Individual kidney glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and the hematocrit (Hct) were measured routinely. Renal irradiation resulted in a progressive decline in GFR, ERPF, and Hct, with minimal values being observed within 12 weeks of irradiation. No change in any of these parameters was noted in the sham-irradiated pigs. The initial morphological change in irradiated glomeruli was leukocyte attachment to capillary endothelial cells 3-6 weeks after irradiation followed by activation and swelling of the endothelial cells. This was followed by pronounced increases in capillary permeability with fluid and erythrocyte, leukocyte, and platelet exudation into the subendothelial/mesangial space. This resulted in compression of glomerular capillary lumina, which occurred concomitantly with the reduction in GFR. By 12 to 15 weeks after irradiation the changes in endothelial cells were less evident. However, mesangial cells exhibited evidence of activation and proliferation accompanied by progressive mesangial expansion and sclerosis. Thus the glomerular capillary endothelial and mesangial cells appear particularly important in the pathogenesis of radiation nephropathy.
12只成年雌性猪的双侧肾脏分别接受单次剂量为9.8 Gy的60Coγ射线照射或假照射。在1 - 4周的间隔时间内进行系列肾脏活检，然后在照射后24周处死。常规测量个体肾脏的肾小球滤过率（GFR）、有效肾血浆流量（ERPF）和血细胞比容（Hct）。肾脏照射导致GFR、ERPF和Hct逐渐下降，在照射后12周内观察到最小值。假照射猪的这些参数均未发生变化。照射后肾小球的初始形态学变化是在照射后3 - 6周白细胞附着于毛细血管内皮细胞，随后内皮细胞活化和肿胀。接着毛细血管通透性显著增加，液体、红细胞、白细胞和血小板渗出到内皮下/系膜间隙。这导致肾小球毛细血管腔受压，这与GFR降低同时发生。照射后12至15周，内皮细胞的变化不太明显。然而，系膜细胞表现出活化和增殖的迹象，伴有系膜逐渐扩张和硬化。因此，肾小球毛细血管内皮细胞和系膜细胞在放射性肾病的发病机制中显得尤为重要。
