Hiraide T, Katsura K, Muramatsu H, Asano G, Katayama Y
The Second Department of Internal Medicine, Nippon Medical School, 1-1-5 Bunkyo-ku, Sendagi, Tokyo 113-8603, Japan. hiraide-tomoharu/
Brain Res. 2001 Aug 10;910(1-2):94-8. doi: 10.1016/s0006-8993(01)02647-6.
Pretreatment of the brain with sublethal ischemia has been reported to induce neuronal resistance to otherwise lethal ischemia, a phenomenon designated as ischemic tolerance. The protective mechanisms of the phenomenon are not known yet, however, recent experimental data suggest the involvement of adenosine receptor activation in the acquisition of tolerance. In this study, the effect of theophylline, a non-selective adenosine receptor antagonist, and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A1 receptor antagonist, were investigated to ascertain if these drugs could cancel the protective effect of ischemic tolerance in the gerbil. DPCPX or theophylline was administered at 3 h after a short preconditioning ischemia, and 21 h later animals were subjected to lethal ischemia of 5 min duration. DPCPX at a dose of 1.0 mg/kg (i.p) and theophylline at a dose of 20 mg/kg (i.p) significantly reduced the protective effect of preconditioning in the CA1 hippocampal neurons. These findings suggest the involvement of adenosine receptor activation for the development of ischemic tolerance phenomenon.
据报道，用亚致死性缺血对大脑进行预处理可诱导神经元对原本致死性缺血产生抗性，这一现象被称为缺血耐受。然而，该现象的保护机制尚不清楚，不过最近的实验数据表明腺苷受体激活参与了耐受性的获得。在本研究中，研究了非选择性腺苷受体拮抗剂茶碱和腺苷A1受体拮抗剂8-环戊基-1,3-二丙基黄嘌呤（DPCPX）的作用，以确定这些药物是否会消除沙土鼠缺血耐受的保护作用。在短暂的预处理缺血后3小时给予DPCPX或茶碱，21小时后对动物进行持续5分钟的致死性缺血。剂量为1.0mg/kg（腹腔注射）的DPCPX和剂量为20mg/kg（腹腔注射）的茶碱显著降低了预处理对海马CA1区神经元的保护作用。这些发现表明腺苷受体激活参与了缺血耐受现象的发生。
