A2A adenosine receptor-mediated inhibition of renal injury and neutrophil adhesion
A2A adenosine receptor-mediated inhibition of renal injury and neutrophil adhesion
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DOI：
10.1152/ajprenal.2000.279.5.f809
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发表时间：
2000-11-01
影响因子：
4.2
通讯作者：
Huynh, LP
中科院分区：
文献类型：
--
作者：
Okusa, MD;Linden, J;Huynh, LP
我们试图确定在缺血-再灌注（I/R）损伤模型中，A（2A）腺苷受体激动剂（A(2A)-ARs）减轻肾组织损伤的机制。DWH-146e是一种选择性a (2A)-AR激动剂，通过渗透微型泵给药于Sprague-Dawley大鼠和C57BL/6小鼠皮下，动物进行I/R。I/R导致血浆肌酐和肾中性粒细胞浸润增加。DWH-146e以10 ng滴注。公斤(1)。Min（-1）使血浆肌酐降低70%，髓外质和皮质中性粒细胞密度降低，再灌注肾髓过氧化物酶活性降低。肾髓过氧化物酶活性与肾损伤程度相关。p -选择素和细胞间粘附分子1 （ICAM-1）的免疫反应性在肾缺血再灌注小鼠的小管周围毛细血管内皮细胞和皮层及髓内外小叶间动脉内皮细胞中最为突出。DWH-146e治疗导致p -选择素和icam -1样免疫反应性明显降低。这些数据与我们的假设一致，即A(2A)-AR激动剂由于对中性粒细胞粘附的抑制作用而限制I/R损伤。
We sought to determine the mechanisms responsible for the reduced renal tissue injury by agonists of A(2A) adenosine receptors (A(2A)-ARs) in models of ischemia-reperfusion (I/R) injury. DWH-146e, a selective A(2A)-AR agonist, was administered subcutaneously to Sprague-Dawley rats and C57BL/6 mice via osmotic minipumps, and animals were subjected to I/R. I/R led to an increase in plasma creatinine and kidney neutrophil infiltration. Infusion of DWH-146e at 10 ng . kg(-1). min(-1) produced a 70% reduction in plasma creatinine as well as a decrease in neutrophil density in outer medulla and cortex and myeloperoxidase activity in the reperfused kidney. Myeloperoxidase activity in kidney correlated with the degree of renal injury. P-selectin and intercellular adhesion molecule 1 (ICAM-1) immunoreactivity were most prominent in endothelial cells of peritubular capillaries and interlobular arteries of cortex and outer and inner medulla of vehicle-treated mice whose kidneys were subjected to I/R. DWH-146e treatment led to a pronounced decrease in P-selectin- and ICAM-1-like immunoreactivity. These data are consistent with our hypothesis that A(2A)-AR agonists limit I/R injury due to an inhibitory effect on neutrophil adhesion.