Jongejan H T, van der Kogel A J, Provoost A P, Molenaar J C
Department of Paediatric Surgery, Erasmus University Rotterdam, The Netherlands.
Radiother Oncol. 1987 Sep;10(1):49-57. doi: 10.1016/s0167-8140(87)80069-5.
The interaction between single low doses of cis-diamminedichloroplatinum(II) (c-DDP) and renal irradiation (7.5, 10, 12.5 Gy) on renal function and systolic blood pressure (SBP) was investigated in young (3-4 weeks old, BW 45-65 g) and adult rats (over 12 weeks old, BW 230-290 g). The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), plasma creatinine, urea and SBP were measured over 24 weeks. Changes in ERPF, plasma creatinine and urea concentrations paralleled GFR changes, but tended to be less pronounced. In young rats, BW and GFR were 10-20% below control values after c-DDP administration (5 mg/kg BW). Irradiation caused a dose-dependent drop in GFR, starting 4 weeks after irradiation in young rats. When c-DDP was given immediately after irradiation to the young rats, the loss of renal function was more pronounced than after either treatment modality alone. Dose-effect curves for a greater than 25% reduction of the GFR relative to controls (ml/min) after 24 weeks gave an ED50 of 9.8 Gy for irradiation alone and 4.6 Gy for irradiation followed by c-DDP. After correction for the drug effect, dose-effect curves were similar for renal irradiation given alone or followed by c-DDP administration in young rats. In adult rats, c-DDP (2.5 mg/kg BW) or irradiation alone did not significantly alter renal function during the follow-up period. Only 12.5 Gy in combination with c-DDP, caused a significant reduction in GFR after 16 weeks in adult rats. In adult rats data were too limited for probit analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了单次低剂量顺二氯二氨铂（II）（c-DDP）与肾脏照射（7.5、10、12.5 Gy）对年轻（3-4周龄，体重45-65 g）和成年大鼠（12周龄以上，体重230-290 g）肾功能和收缩压（SBP）的相互作用。在24周内测量肾小球滤过率（GFR）、有效肾血浆流量（ERPF）、血浆肌酐、尿素和SBP。ERPF、血浆肌酐和尿素浓度的变化与GFR变化平行，但变化趋势不太明显。在年轻大鼠中，给予c-DDP（5 mg/kg体重）后，体重和GFR比对照值低10-20%。照射导致年轻大鼠照射后4周开始GFR呈剂量依赖性下降。当年轻大鼠照射后立即给予c-DDP时，肾功能丧失比单独使用任何一种治疗方式都更明显。24周后相对于对照（ml/min）GFR降低大于25%的剂量-效应曲线显示，单独照射的ED50为9.8 Gy，照射后给予c-DDP的ED50为4.6 Gy。校正药物效应后，年轻大鼠单独给予肾脏照射或照射后给予c-DDP的剂量-效应曲线相似。在成年大鼠中，c-DDP（2.5 mg/kg体重）或单独照射在随访期间未显著改变肾功能。仅12.5 Gy与c-DDP联合使用，在成年大鼠16周后导致GFR显著降低。在成年大鼠中，数据有限，无法进行概率分析。（摘要截断于250字）
