吡那地尔对低氧低糖诱导神经细胞凋亡的抑制作用

INHIBITORY EFFECTS OF PINACIDIL ON APOPTOSIS OF PRIMARY CULTURED CORTICAL NEURONS INDUCED BY HYPOXIA-HYPOGLYCEMIA

目的 探讨ATP敏感性钾通道 (KATP)开放剂吡那地尔 (Pin)对低氧低糖再复氧诱导的大鼠皮质神经细胞凋亡的影响。方法 用电镜和流式细胞分析技术 ,检测原代培养的大鼠皮质神经细胞凋亡。结果 低氧低糖再复氧可诱导大鼠皮质神经细胞凋亡。Pin ( 10 - 5,10 - 6 ,10 - 7mol·L- 1 ) 3个剂量组均能降低凋亡细胞百分率 ,以 10 - 5mol·L- 1 组效果最好。上述作用可被KATP特异性阻断剂格列苯脲 (Gli)所拮抗。结论 Pin对低氧低糖再复氧诱导的大鼠皮质神经细胞凋亡有明显的抑制作用 ,提示KATP通道在调控细胞凋亡的过程中可能起着重要的作用。

AIM To investigate the effects of ATP-sensitive potassium channel (K ATP ) opener pinacidil (Pin) on apoptosis of primary cultured cortical neurons induced by hypoxia-hypoglycemia and reoxygenation. METHODS Apoptosis was measured using electron microscope and flow cytometric analysis technique. RESULTS Hypoxia-hypoglycemia and reoxygenation was shown to induce apoptosis of cortical neurons in primary culture. Pin (10 -5 , 10 -6 , 10 -7 mol·L -1 ) was found to decrease the percent of apoptosis. Pin (10 -5 mol·L -1 ) was found to improve ultrastructural features of apoptosis of cortical neurons induced by hypoxia-hypoglycemia and reoxygenation. These effects were reversed by glibenclamide (Gli), the specific antagonist of K ATP . CONCLUSION Pin showed inhibitory effects on apoptosis of cortical neurons induced by hypoxia-hypoglycemia and reoxygenation.These results indicate that K ATP plays important role in regulating the process of apoptosis.