脑预缺血引起大鼠海马细胞膜腺苷受体数量和亲和力升高及其对神经元的保护作用

Increase in amount and affinity of adenosine receptor in rat hippocampal cellular membranes induced by cerebral ischemic preconditioning and its protective effects on the neurons

采用放射性配基结合法 ,测定大鼠全脑缺血后海马细胞膜腺苷 (adenosine,ADO)受体数量及亲和力的变化 ,以探讨其与脑缺血耐受形成之间的关系。发现缺血 6min即可导致海马组织明显的神经元延迟性死亡 (de layedneurondeath ,DND) ,缺血 3min不足以引起海马组织明显的DND ;而经过 3min预缺血处理 ,可明显减轻间隔1d后 6min缺血引起的海马DND (P <0 0 1)。与此相对应 ,缺血 3min再灌 1和 3d时 ,ADO受体数量及亲和力明显高于sham组 (P <0 0 5 ) ,而缺血 6min再灌 1和 3d时 ,ADO受体数量明显低于sham组 (P <0 0 5 ) ,但亲和力高于sham组 (P <0 0 5 )。与单纯 6min缺血再灌 4h、1和 3d时相比 ,3min预缺血 + 6min缺血 (间隔 1d)再灌后 ,ADO受体数量及亲和力均显著升高 (P <0 0 5 )。这些结果表明 ,脑预缺血处理可使大鼠海马细胞膜ADO受体数量增多 ,亲和力增强 ,并能对抗损伤性缺血引起的ADO受体数量减少 ,提示腺苷受体数量及亲和力的变化在脑缺血耐受形成过程中发挥了重要的作用。

To determine the role of adenosine (ADO) receptor in the induction of brain ischemic tolerance, changes in amount and affinity of ADO receptor in rat hippocampal cellular membranes after transient ischemia were investigated using radioligand binding method. Ischemia for 6 min resulted in an apparent delayed neuron death (DND) in the hippocampus, while ischemia for 3 min did not cause DND. Preconditioning ischemia for 3 min could apparently decrease DND caused by ischemia for 6 min after the preconditioning at an interval of 1 d reperfusion. In correspondence with the histological changes, ischemia for 3 min caused an increase in amount and affinity of ADO receptor at 1 or 3 days after reperfusion ( P <0 05 vs sham), while ischemia for 6 min caused a decrease in the amount and an increase in the affinity ( P <0 05 vs sham). Compared with the rats suffering from ischemia for 6 min followed by reperfusion for 4 h and 1 or 3 d, the amount and affinity of ADO receptor increased in rats with preconditioning ischemia (3 min) 1 d before the ischemia for 6 min The above results showed that cerebral ischemic preconditioning increased the amount and affinity of ADO receptor in hippocampal cellular membranes, and resisted the down regulating of ADO receptor caused by severe ischemia, suggesting an important role of the increase in amount and affinity of ADO receptor in the induction of brain ischemic tolerance.