Department of Nuclear Medicine, University of Munich, Munich, 81377, Germany.
EJNMMI Res. 2012 Jan 20;2:2. doi: 10.1186/2191-219X-2-2.
Experimental models are essential tools in the development and evaluation of novel treatment options, but the preclinical model of renal ischemia-reperfusion injury is limited to the retrieval of (very) early functional data, leaving the pivotal long-term outcome unknown. The present study applies technetium-99m-mercapto-acetyl-tri-glycine [99mTc-MAG3] scintigraphy for the longitudinal follow-up examination of long-term kidney function after renal ischemia-reperfusion injury.
Unilateral warm ischemia was induced in scid beige mice by vascular clamping of the kidney hilum for 40 min. 99mTc-MAG3 scintigraphy was performed prior to injury, 8 and 14 days post ischemia. The fractional uptake rate [FUR] was calculated from scintigraphy data as a measure of renal clearance.
FUR demonstrated a significant functional impairment of the ischemic kidney 8 and 14 days after injury (P < 0.05 vs. baseline), while contralateral non-ischemic kidneys showed no significant changes. In histological analysis, ischemic kidneys exhibited tubular dilatation and cytoplasmic degeneration as signs of hypoxia without any evidence for necrosis.
FUR enables the detection of renal dysfunction and longitudinal long-term follow-up examination in the same individual. Our model may facilitate preclinical therapy evaluation for the identification of effective renoprotective therapies.
实验模型是开发和评估新型治疗方案的重要工具，但肾缺血再灌注损伤的临床前模型仅限于获取（非常）早期的功能数据，关键的长期结果仍不清楚。本研究应用锝-99m-巯基乙酰三甘氨酸[99mTc-MAG3]闪烁显像术对肾缺血再灌注损伤后长期肾功能进行纵向随访检查。
通过血管夹夹闭肾门使 scid beige 小鼠单侧肾脏产生 40 分钟的温热性缺血。在损伤前、缺血后 8 天和 14 天进行 99mTc-MAG3 闪烁显像术。通过闪烁显像术数据计算摄取分数率[FUR]，作为肾功能清除率的衡量指标。
FUR 显示缺血肾脏在损伤后 8 天和 14 天出现明显的功能障碍（P<0.05 与基线相比），而对侧非缺血肾脏没有明显变化。组织学分析显示，缺血肾脏出现了管状扩张和细胞质变性，提示存在缺氧，但没有坏死的证据。
FUR 能够检测肾功能障碍，并在同一个体中进行纵向长期随访检查。我们的模型可能有助于临床前治疗评估，以确定有效的肾保护治疗方法。
