Sugino H, Shimada H, Tsuchimoto K
Division of Pathophysiology, Center for Clinical Pharmacy and Clinical Sciences, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Jpn J Pharmacol. 2001 Oct;87(2):134-42. doi: 10.1254/jjp.87.134.
The protective effect of a brief episode of ischemic preconditioning was examined at an early phase of ischemic-reperfusion injury in the rat kidney. Rats were subjected to 50 min of left renal artery occlusion followed by 120 min of reperfusion. Ischemic preconditioned rats were subjected to preconditioning with two cycles of 3-min ischemia and 5-min reperfusion (IPC). Ischemic-reperfusion injury led to a low recovery of the glomerular filtration rate (GFR). Overt morphological changes, consisting of blood trapping and tubular collapse, were seen. IPC improved the recovery of GFR and renal morphology. The IPC effect was not blocked by 8-(p-sulfophenyl)-theophylline (SPT), a non-selective adenosine receptor antagonist, by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective A1-receptor antagonist, or by 3,7-dimethyl-1-propargylxanthine (DMPX), a selective A2-receptor antagonist. Intravenous infusion of adenosine (30 microg/min per rat, for 5 min) prior to the 50-min occlusion improved the recovery of GFR, and this protection of GFR was blocked by SPT. Thus, both IPC and exogenous adenosine attenuated ischemic-reperfusion injury of the kidney. However, because three adenosine receptor antagonists failed to abolish the protective effect of IPC, there is no evidence to indicate that activation of adenosine receptors contributes to the IPC effect in the kidney.
在大鼠肾脏缺血再灌注损伤的早期阶段,研究了短暂缺血预处理的保护作用。对大鼠进行50分钟的左肾动脉闭塞,随后进行120分钟的再灌注。缺血预处理的大鼠接受两个周期的3分钟缺血和5分钟再灌注(IPC)预处理。缺血再灌注损伤导致肾小球滤过率(GFR)恢复较低。可见明显的形态学变化,包括血液淤滞和肾小管塌陷。IPC改善了GFR和肾脏形态的恢复。IPC的作用未被非选择性腺苷受体拮抗剂8-(对磺基苯基)茶碱(SPT)、选择性A1受体拮抗剂1,3-二丙基-8-环戊基黄嘌呤(DPCPX)或选择性A2受体拮抗剂3,7-二甲基-1-丙炔基黄嘌呤(DMPX)阻断。在50分钟闭塞前静脉输注腺苷(每只大鼠30微克/分钟,持续5分钟)可改善GFR的恢复,并且这种对GFR的保护作用被SPT阻断。因此,IPC和外源性腺苷均减轻了肾脏的缺血再灌注损伤。然而,由于三种腺苷受体拮抗剂未能消除IPC的保护作用,没有证据表明腺苷受体的激活有助于肾脏中的IPC作用。