The role of adenosine A1 receptor system in the delayed protective effects of ischemic preconditioning in brain ischemia in rabbits / 中华麻醉学杂志

ABSTRACT

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-cyclopentyl-1,3-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 70% 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 .