Section of Experimental Medicine, Department of Medicine, Georgia Health Sciences University, Augusta, GA 30912, USA.
Am J Physiol Renal Physiol. 2012 Nov 1;303(9):F1333-40. doi: 10.1152/ajprenal.00406.2012. Epub 2012 Aug 29.
Renal ischemia-reperfusion injury is a major cause of acute kidney injury that carries a high mortality rate and increases the risk of later development of hypertension and chronic kidney disease. Although mouse models have contributed much to our understanding of the mechanisms involved, studying aspects of the injury process in vivo remains technically challenging. This study validates the use of noninvasive ultrasound imaging to assess both renal perfusion and vascular adhesion molecule expression following 1-h unilateral renal ischemia in male and female mice. Pulsed-wave Doppler measurements of renal arterial blood velocity revealed renal perfusion recoveries of 56 ± 9% in male and 69 ± 10% in female mice 1 h after the commencing of reperfusion, which is similar to what we have previously published using conventional invasive methodology. At 24 h postischemia, renal perfusion was 40 ± 8% in male and 46 ± 7% in female mice, representing a further significant reduction of perfusion (P(Time) < 0.001). Using ultrasound imaging of a P-selectin-targeted contrast agent, a significant increase in vascular P-selectin protein expression was observed after 1-h reperfusion in the cortex of the postischemic compared with contralateral kidney in both male and female mice (18 ± 5 vs. 3 ± 3 intensity units in male and 30 ± 6 vs. 0 ± 4 in female mice, P(Ischemia) < 0.01). An approximately sixfold increase in P-selectin mRNA was observed ex vivo in the renal vasculature of male and female mice at this time point (P < 0.01). In conclusion, ultrasound represents an effective and noninvasive method for the measurement of both renal perfusion and vascular adhesion molecule expression in mice.
肾缺血再灌注损伤是急性肾损伤的主要原因，其死亡率高，并增加了高血压和慢性肾脏病发展的风险。尽管小鼠模型对我们理解相关机制做出了重大贡献，但在体内研究损伤过程的某些方面仍然具有技术挑战性。本研究通过非侵入性超声成像验证了其在雄性和雌性小鼠单侧肾缺血 1 小时后评估肾脏灌注和血管黏附分子表达的应用。肾脏动脉血流的脉冲波多普勒测量显示，在再灌注开始后 1 小时，雄性和雌性小鼠的肾脏灌注恢复分别为 56 ± 9%和 69 ± 10%，与我们之前使用传统侵入性方法发表的数据相似。在缺血后 24 小时，雄性和雌性小鼠的肾脏灌注分别为 40 ± 8%和 46 ± 7%，这代表灌注进一步显著减少（P（时间）<0.001）。使用 P-选择素靶向对比剂的超声成像，在雄性和雌性小鼠的缺血后肾脏皮质中，与对侧肾脏相比，在 1 小时再灌注后观察到血管 P-选择素蛋白表达显著增加（18 ± 5 与 3 ± 3 强度单位；30 ± 6 与 0 ± 4，P（缺血）<0.01）。在此时点，雄性和雌性小鼠的肾脏血管中观察到 P-选择素 mRNA 约增加了六倍（P < 0.01）。总之，超声是测量小鼠肾脏灌注和血管黏附分子表达的有效且非侵入性方法。
