Kramer H J, Mohaupt M G, Pinoli F, Bäcker A, Meyer-Lehnert H, Schlebusch H
Department of Medicine, University of Bonn, Germany.
J Am Soc Nephrol. 1993 Jul;4(1):50-7. doi: 10.1681/ASN.V4150.
To investigate the potential pathogenetic and therapeutic roles of thromboxane A2 (TXA2) and its receptor blockade, respectively, in the early phase of ischemic acute renal failure (ARF), renal function, TXB2 excretion, and the effects of the specific TXA2 receptor antagonist sulotroban (SU) in a model of unilateral renal artery occlusion in conscious female Sprague-Dawley rats were studied. Occlusion of the left renal artery for 1 h in untreated (i.e., vehicle-treated) rats (N = 8) resulted in oliguric ARF. In SU-treated rats (N = 8), the drug was given as an i.v. bolus of 5 mg/kg body wt, followed by a continuous infusion of 0.5 mg/min.kg body wt from 1 h before and during ischemia and for 6 h after reflow. After 1 h of ischemia, urine volume of left ischemic kidneys from untreated rats had decreased from 13.2 +/- 2.8 to 1.0 +/- 0.3 and 0.5 +/- 0.2 microL/min.100 g at 2 and 6 h of reflow, respectively, and GFR had decreased from 0.32 +/- 0.04 mL/min.100 g body wt to undetectable values. At 6 h of reflow, medullary Na-K-ATPase was slightly (P < 0.05) reduced in left ischemic kidneys, whereas medullary and papillary enzyme activities were compensatorily increased (P < 0.01) in right intact kidneys. The ADP/O ratio of cortical mitochondria was 41% (P < 0.05) and ATP synthesis was 77% (P < 0.01) lower than in right intact kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
为了分别研究血栓素A2（TXA2）及其受体阻断在缺血性急性肾衰竭（ARF）早期阶段的潜在致病和治疗作用，我们在清醒的雌性Sprague-Dawley大鼠单侧肾动脉闭塞模型中，研究了肾功能、TXB2排泄以及特异性TXA2受体拮抗剂舒洛地尔（SU）的作用。未治疗（即给予赋形剂）的大鼠（N = 8）左肾动脉闭塞1小时导致少尿型ARF。在SU治疗的大鼠（N = 8）中，药物以5 mg/kg体重的静脉推注给药，随后在缺血前1小时和缺血期间以及再灌注后6小时以0.5 mg/min·kg体重的速度持续输注。缺血1小时后，未治疗大鼠左缺血肾脏的尿量在再灌注2小时和6小时时分别从13.2±2.8降至1.0±0.3和0.5±0.2 μL/min·100 g，肾小球滤过率（GFR）从0.32±0.04 mL/min·100 g体重降至无法检测的值。在再灌注6小时时，左缺血肾脏的髓质钠钾ATP酶略有降低（P < 0.05），而右完整肾脏的髓质和乳头酶活性则代偿性增加（P < 0.01）。皮质线粒体的ADP/O比值比右完整肾脏低41%（P < 0.05），ATP合成比右完整肾脏低77%（P < 0.01）。（摘要截断于250字）
