Robbins M E, Hopewell J W
CRC Normal Tissue Radiobiology Research Group, University of Oxford, Churchill Hospital, U.K.
Radiother Oncol. 1988 Mar;11(3):253-62. doi: 10.1016/0167-8140(88)90008-4.
Irradiation of a single kidney in the pig with relatively low doses of X-rays, in the order of 8 Gy, produces a pronounced reduction in both glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). This apparent high radiosensitivity may be due, in part, to the compensatory hypertrophy displayed by the contralateral unirradiated kidney. This could suppress any potential for recovery by the irradiated kidney. To test this hypothesis, both kidneys of 14-week-old Large White pigs were sequentially irradiated with single doses of 250 kV X-rays, in the range 8.8 to 12.6 Gy. Sequential measurements of individual kidney GFR and ERPF were made for periods up to 24 weeks after irradiation. Time-related changes in haematocrit (Hct) were also studied. Two weeks after irradiation, GFR and ERPF increased markedly in all irradiated kidneys; levels then declined in a dose-dependent manner. Following a dose of 8.8 Gy renal haemodynamics returned to control values within 4 weeks of irradiation and remained essentially constant throughout the study. After higher doses, GFR and ERPF decreased markedly and remained below control values up to 24 weeks after irradiation. Associated with these changes in renal haemodynamics was a fall in Hct within 3 weeks of irradiation, with minimal levels being found approximately 8 weeks after irradiation. Although there was some recovery between weeks 12 and 24, Hct values remained below those of age-matched controls. At all doses the mean functional status of irradiated kidneys in animals in which both kidneys were irradiated (BI) was significantly greater than that previously observed in the irradiated kidney of pigs in which only one kidney was irradiated (UI). Moreover, in BI pigs there appeared to be a marked imbalance between the contribution each kidney makes to the total renal function. In terms of ERPF, the functional status of the right kidney, relative to that of the left kidney, showed a dose-related decline. These findings support the hypothesis that the compensatory response exhibited by the contralateral unirradiated kidney in UI pigs suppresses the potential for functional recovery by the irradiated kidney. The findings also indicate that individual kidneys in the same animal may differ in their response to a similar nephrotoxic insult.
用相对低剂量的X射线（约8 Gy）照射猪的单个肾脏，会使肾小球滤过率（GFR）和有效肾血浆流量（ERPF）均显著降低。这种明显的高放射敏感性可能部分归因于对侧未受照射的肾脏所表现出的代偿性肥大。这可能会抑制受照射肾脏的任何恢复潜力。为了验证这一假设，对14周龄的大白猪的双侧肾脏依次进行单剂量250 kV X射线照射，剂量范围为8.8至12.6 Gy。在照射后长达24周的时间内，对各个肾脏的GFR和ERPF进行连续测量。还研究了血细胞比容（Hct）随时间的变化。照射后两周，所有受照射肾脏的GFR和ERPF均显著增加；随后水平以剂量依赖的方式下降。给予8.8 Gy剂量后，肾脏血流动力学在照射后4周内恢复到对照值，并在整个研究过程中基本保持恒定。给予更高剂量后，GFR和ERPF显著下降，并在照射后24周内一直低于对照值。与这些肾脏血流动力学变化相关的是，照射后3周内Hct下降，在照射后约8周时达到最低水平。尽管在第12周和第24周之间有一定程度的恢复，但Hct值仍低于年龄匹配的对照组。在所有剂量下，双侧肾脏均受照射的动物（BI）中受照射肾脏的平均功能状态明显高于先前在仅一侧肾脏受照射的猪（UI）中观察到的受照射肾脏的功能状态。此外，在BI猪中，每个肾脏对总肾功能的贡献之间似乎存在明显的不平衡。就ERPF而言，右肾相对于左肾的功能状态呈现出剂量相关的下降。这些发现支持了以下假设：UI猪中对侧未受照射的肾脏所表现出的代偿反应会抑制受照射肾脏的功能恢复潜力。这些发现还表明，同一动物体内的各个肾脏对类似的肾毒性损伤的反应可能不同。
