腺苷A1受体系统在兔脑预缺血延迟相保护效应中的作用

目的 探讨腺苷A1受体系统在兔脑预缺血延迟相保护效应中的作用。方法 股动脉放血至平均动脉压35－40mmHg时，阻断双侧颈总动脉诱导脑缺血。脑缺血3min存活3d（预缺血处理）后、脑缺血10min（预缺血延迟相保护模型）；用腺苷A1受体激动剂氮6－环戊基腺苷（CPA）代替预缺血处理，用其拮抗剂8－环戊基－1，3－二丙基黄嘌呤（DPCPX）阻断该受体；免疫组化分析热休克蛋白70（SHP70）表达。观察缺血3d后海马CA1区正常神经密度和HSP70的表达。结果 （1）CPA能减轻脑缺血损害，但其保护作用不如预缺明显（约占后者的70％），DPCPX阻断该受体后，预缺血延迟相保护作用消失；（3）3min脑预缺血神经元无损害，但伴HSP70明显表达；DPCPX阻断腺苷A1受体后，3min脑预缺血发生明显损害，且HSP70表达明显削弱。结论 （1）预缺血延迟相保护作用与腺苷A1受体系统激活有关；（2）DPCPX阻断预缺血延迟相保护作用的机制与削弱HSP70表达有关。

he role of adenosine A1 receptor system in the delayed protective effects of ischemic preconditioning in brain ischemia in rabbits

Objective To determine the role of adenosine A1 receptor system in the delayed protective effects of ischemic preconditioning (IPC) in brain ischemia. Methods Thirty-five rabbits weighing 2-2.5kg were randomly divided into 7 groups: control (group Ⅰ), 3-min ischemia (group Ⅱ), 10-min ischemia (group Ⅲ), IPC (group Ⅳ), N6-cyclopentyladenosine (CPA)(group V), 8-cyclopentyl1,3-dipropylxanthine (DPCPX)+ IPC(group Ⅵ), and DPCPX + 3-min ischemia (group Ⅶ). Cerebral ischemia was produced by occlusion of both carotid arteries in combination withdrawing blood to maintain MAP at 35-40 mmHg. After 3-min IPC and 3 days of recovery, cerebral ischemia was induced and lasted 10 min (model of delayed protective effects of IPC). Adenosine A1 receptor agonist CPA or antagonist DPCPX was used instead of IPC to evaluate the role of adenosine A1 receptor in the delayed protective effects of IPC. The expression of heat shock protein 70 (HSP70) was analyzed by immunohistochemistry. Neurons density and expression of HSP70 in the hippocampal CA1 region were examined and measured 3 days later. Results (1) CPA could reduce cerebral ischemic injury, but the effects of CPA were not as good as those of IPC (about 7096 of IPC). After adenosine A1 receptors being blocked by DPCPX the delayed protective effects of IPC disappeared. (2) 3-min ischemia alone did not cause neuronal injury but induced obvious expression of HSP70. DPCPX not only could make 3-min ischemia cause injury but also reduce the expression of HSP70. Conclusions ( 1 ) The delayed protective effects of IPC is related with activation of adenosine A1 receptor system. (2) One of the mechanisms of the blocking effects of DPCPX may be due to the reduction in expression of HSP70 .