Ochodnický Peter, de Zeeuw Dick, Henning Robert H, Kluppel C Alex, van Dokkum Richard P E
Department of Clinical Pharmacology, University Medical Centre Groningen, The Netherlands.
J Am Soc Nephrol. 2006 Apr;17(4 Suppl 2):S49-52. doi: 10.1681/ASN.2005121322.
It was demonstrated that individual renal endothelial dilatory function of the healthy rat predicts susceptibility to subsequent renal damage induced by 5/6 nephrectomy. In addition, it is reported that myocardial infarction (MI) that was performed upon unilateral nephrectomy (UNx) induced highly variable renal damage. Therefore, whether the variability in renal damage after MI could be explained by the variation in individual renal endothelial function before the induction of injury was studied. Endothelium-dependent relaxation to acetylcholine was investigated in vitro in small arteries that were isolated from the extirpated kidney at UNx. MI was induced 1 wk after UNx by ligation of the left coronary artery. Proteinuria and systolic BP were evaluated weekly for 16 wk thereafter using metabolic cages and the tail-cuff method, respectively. Upon termination of the study, focal glomerulosclerosis was evaluated by histology as an additional marker of renal damage. After MI, nephrectomized male Wistar rats (n = 15) gradually developed variable proteinuria, ranging from 20 to 507 mg/24 h at week 16, with an average systolic BP of 131 +/- 7 mmHg. The individual renal endothelial function of the healthy rats predicted the extent of renal damage in terms of proteinuria (r = -0.62, P = 0.008) and focal glomerulosclerosis (r = -0.70, P = 0.003). The individual level of renal endothelial function in the healthy rat is able to predict the severity of renal damage that is induced by MI. Further exploration of the underlying mechanisms may lead to discovery of preventive renoprotective therapies.
结果表明，健康大鼠的个体肾内皮舒张功能可预测后续5/6肾切除诱导的肾损伤易感性。此外，据报道，单侧肾切除（UNx）后发生的心肌梗死（MI）会导致高度可变的肾损伤。因此，研究了MI后肾损伤的变异性是否可以用损伤诱导前个体肾内皮功能的变化来解释。在UNx时从切除的肾脏分离的小动脉中体外研究乙酰胆碱引起的内皮依赖性舒张。UNx后1周通过结扎左冠状动脉诱导MI。此后16周每周分别使用代谢笼和尾袖法评估蛋白尿和收缩压。研究结束时，通过组织学评估局灶性肾小球硬化作为肾损伤的额外标志物。MI后，肾切除的雄性Wistar大鼠（n = 15）逐渐出现可变的蛋白尿，在第16周时范围为20至507 mg/24 h，平均收缩压为131±7 mmHg。健康大鼠的个体肾内皮功能在蛋白尿（r = -0.62，P = 0.008）和局灶性肾小球硬化（r = -0.70，P = 0.003）方面可预测肾损伤程度。健康大鼠的个体肾内皮功能水平能够预测MI诱导的肾损伤严重程度。对潜在机制的进一步探索可能会导致发现预防性肾保护疗法。
