Protective effects of renal ischemic preconditioning and adenosine pretreatment:: role of A1 and A3 receptors
Protective effects of renal ischemic preconditioning and adenosine pretreatment:: role of A1 and A3 receptors
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DOI：
10.1152/ajprenal.2000.278.3.f380
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发表时间：
2000-03-01
影响因子：
4.2
通讯作者：
Emala, CW
中科院分区：
文献类型：
--
作者：
Lee, HT;Emala, CW
主动脉和肾移植手术期间的肾脏缺血和再灌注会导致缺血再灌注损伤。缺血前的缺血预处理和腺苷输注可以保护心肌和骨骼肌免受缺血再灌注损伤，但这些保护现象尚未在肾脏中得到证实。大鼠被随机分为假手术、45分钟肾缺血、缺血预处理（4个周期的8分钟肾缺血和5分钟再灌注，然后45分钟肾缺血）、45分钟肾缺血前全身腺苷预处理，或45分钟肾缺血前用选择性腺苷受体亚型激动剂或拮抗剂预处理。 45 分钟的肾缺血和 24 小时的再灌注导致血尿素氮和肌酐显着升高。缺血预处理和腺苷预处理可保护肾功能并改善肾脏形态。 A(1) 腺苷受体激活模拟和 A(1) 腺苷拮抗作用可阻断腺苷诱导的保护。此外，肾缺血前A(3)腺苷受体激活会加重肾缺血再灌注损伤，而A(3)腺苷受体拮抗作用可保护肾功能。我们首次证明，在缺血性损伤通过 A(1) 腺苷受体激活保护肾功能之前，可以对大鼠肾脏进行预处理以减轻缺血再灌注损伤和腺苷输注。我们的数据表明，A(1) 腺苷激动剂和 A(3) 腺苷拮抗剂可能在肾缺血不可避免的情况下具有临床有益意义。
Renal ischemia and reperfusion during aortic and renal transplant surgery result in ischemic-reperfusion injury. Ischemic preconditioning and adenosine infusion before ischemia protect against ischemic-reperfusion injury in cardiac and skeletal muscle, but these protective phenomena have not been demonstrated in the kidney. Rats were randomized to sham operation, 45-min renal ischemia, ischemic preconditioning with four cycles of 8-min renal ischemia and 5-min reperfusion followed by 45-min renal ischemia, systemic adenosine pretreatment before 45-min renal ischemia, or pretreatments with selective adenosine receptor subtype agonists or antagonists before 45-min renal ischemia. Forty-five minutes of renal ischemia followed by 24 h of reperfusion resulted in marked rises in blood urea nitrogen and creatinine. Ischemic preconditioning and adenosine pretreatment protected renal function and improved renal morphology. A(1) adenosine receptor activation mimics and A(1) adenosine antagonism blocks adenosine-induced protection. In addition, A(3) adenosine receptor activation before renal ischemia worsens renal ischemic-reperfusion injury, and A(3) adenosine receptor antagonism protects renal function. We demonstrate for the first time that rat kidneys can be preconditioned to attenuate ischemic-reperfusion injury and adenosine infusion before ischemic insult protects renal function via A(1) adenosine receptor activation. Our data suggest that an A(1) adenosine agonist and A(3) adenosine antagonist may have clinically beneficial implications where renal ischemia is unavoidable.