Zhang Y
Department of Neurosurgery, Nantong Medical College Second Affiliated Hospital, Nantong, Jiangsu Province 226001, PR China.
Neuroscience. 2004;125(3):625-31. doi: 10.1016/j.neuroscience.2004.02.011.
Clonidine, a alpha(2)-adrenergic receptor agonist, has been demonstrated to be neuroprotective when administered during ischemia. It is not known whether clonidine can precondition brain against ischemia. We examined this possibility using a transient forebrain ischemia model. Rats received 40 microg/kg of clonidine intraperitoneally at 6, 18, 24 and 72 h as well as 1 week before the forebrain ischemia that was produced by bilateral common carotid arterial occlusion combined with hemorrhagic hypotension to mean arterial pressure 50 mm Hg for 30 min. They were intubated and ventilated with a gas mixture of 1.0% halothane in 30% O(2)/balance air during the procedure. Rats that received clonidine at 6, 18 and 24 h before the ischemia had significantly improved neurological deficit scores and reduced infarct sizes evaluated 3 days after the ischemia. A selective alpha(2)-adrenoceptor antagonist, yohimbine, abolished the neuroprotective effects of clonidine preconditioning. We conclude that there is time window for clonidine preconditioning to be neuroprotective and that alpha(2)-adrenoceptors are important in mediating clonidine preconditioning-induced neuroprotection.
可乐定是一种α₂-肾上腺素能受体激动剂，已证明在缺血期间给予时具有神经保护作用。尚不清楚可乐定是否能对脑进行缺血预处理。我们使用短暂性前脑缺血模型研究了这种可能性。在由双侧颈总动脉闭塞联合出血性低血压使平均动脉压降至50 mmHg持续30分钟所产生的前脑缺血前6小时、18小时、24小时、72小时以及1周时，大鼠腹腔注射40 μg/kg可乐定。在手术过程中，它们通过在含30%氧气/其余为空气的混合气体中加入1.0%氟烷进行插管和通气。在缺血前6小时、18小时和24小时接受可乐定的大鼠，在缺血后3天评估时神经功能缺损评分显著改善，梗死面积减小。一种选择性α₂-肾上腺素能受体拮抗剂育亨宾消除了可乐定预处理的神经保护作用。我们得出结论，可乐定预处理具有神经保护作用存在时间窗，并且α₂-肾上腺素能受体在介导可乐定预处理诱导的神经保护中起重要作用。
