Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Jpn J Radiol. 2010 Feb;28(2):123-31. doi: 10.1007/s11604-009-0396-2. Epub 2010 Feb 26.
The aim of this study was to investigate age-dependent cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced computed tomography (DCE-CT).
The DCE-CT studies were performed in 23 rats aged 4 weeks (n = 6), 6 weeks (n = 6), 8 weeks (n = 6), and 24 weeks (n = 5) on days 0, 2, 4, and 7. The rats were given intraperitoneally cisplatin 3.6 mg/kg body weight (BW) on day 0. The contrast clearance per unit renal volume (K (1)) was estimated using the Patlak model, and that of the entire kidney (K) was obtained by multiplying K(1) by the renal volume (V).
On day 0, the K(1) value increased up to 8 weeks and dropped thereafter. The V and K values increased with age. The K value per unit BW was maximum at 4 weeks, remained relatively unchanged between 6 and 8 weeks, and dropped thereafter. The BW, K(1), and K values normalized by those on day 0 became lower in old rats than in young ones, and the differences among rats of different ages became greater with days after cisplatin injection, indicating that the cisplatin-induced nephrotoxicity becomes more severe with age.
This study demonstrated the existence of age-dependent difference in cisplatin-induced nephrotoxicity in rats.
本研究旨在使用动态对比增强 CT（DCE-CT）研究年龄依赖性顺铂诱导的大鼠肾毒性。
在 4 周龄（n=6）、6 周龄（n=6）、8 周龄（n=6）和 24 周龄（n=5）的 23 只大鼠中进行 DCE-CT 研究，分别在 0、2、4 和 7 天进行。大鼠于第 0 天腹腔内给予 3.6mg/kg 体重的顺铂。使用 Patlak 模型估计单位肾体积的对比清除率（K（1）），并通过将 K（1）乘以肾体积（V）获得整个肾脏的 K 值。
在第 0 天，K（1）值增加至 8 周龄，此后下降。V 和 K 值随年龄增加而增加。单位 BW 的 K 值在 4 周龄时最大，在 6 至 8 周龄之间相对不变，此后下降。经顺铂注射后天数校正的 BW、K（1）和 K 值在老年大鼠中低于年轻大鼠，并且不同年龄大鼠之间的差异随着顺铂注射后天数的增加而增大，表明顺铂诱导的肾毒性随年龄的增长而加重。
本研究表明，在大鼠中存在顺铂诱导的肾毒性的年龄依赖性差异。
