吡那地尔对缺氧缺糖损伤神经细胞的保护作用  

Protective effects of Pinacidil on neurons in rat after anoxic/hypoglycemic damage

作　　者：王华[1] 陈宝芳[1] 李涛[1] 麦根荣[2] 

机构地区：[1]湖北省郧阳医学院附属太和医院儿科 [2]武汉大学人民医院儿科

出　　处：《中华围产医学杂志》2005年第2期120-123,共4页Chinese Journal of Perinatal Medicine

摘　　要：目的　探讨ATP敏感性钾通道(KATP)开放剂吡那地尔(Pinacidil,Pin)对体外培养大鼠大脑皮层神经细胞缺氧缺糖损伤的保护作用。　方法　取培养10 d神经细胞,建立神经细胞缺氧缺糖损伤模型。实验分正常对照组、模型对照组、给药组(Pin和 Pin+Gli处理组),观察缺氧缺糖 4、8、16 h,再复氧24 h后神经细胞死亡率、乳酸脱氢酶(LDH)漏出量和细胞凋亡率的变化,并观察 Pin及KATP通道阻断剂格列苯脲(Gli)对其影响。　结果　经缺氧缺糖损伤后神经细胞死亡率、LDH%和细胞凋亡率均显著升高,Pin干预后,细胞死亡率(4 h: 21.42±3.68和14.83±2.94; 8 h: 36.58±6.14和19.25±3.33; 16 h: 49.17±8.3和28.64±6.4, P值均<0.01)、LDH%(4 h: 26.9±6.1和13.2±4.1; 8 h: 31.4±4.9和18.7±5.3; 16 h: 47.7±6.5和28.1±6.8, P值均<0.01)和细胞凋亡率(16 h: 42±7.8和20.4±5.5, P<0.01)均显著下降,Gli能对抗 Pin这种保护作用。　结论　KATP开放剂Pin具有直接的神经保护作用,其发挥保护作用的机制与其抑制神经细胞凋亡有关。Objective To investigate the protective effects of ATP-sensitive potassium channel (K (ATP)) opener (Pinacidil) on cultured cortical neurons in newborn rats after anoxic/hypoglycemic damage. Methods Neurons were exposed to anoxic/hypoglycemic condition for 4 h,8 h,16 h, after being cultured for 10 days. All cultured neurons were divided into 4 groups: normal control group, model control group, Pinacidil (Pin) group and Pin plus Glibenclamide (Gli) group. The cell mortality, quantity of LDH and the percentage of neuron apoptosis in each group were determined. Results Pinacidil (10^(-6)mol/L ) reduced the percentage of cell death(4 h:21.42±3.68 vs 14.83±2.94; 8 h:36.58±6.14 vs 19.25±3.33; 16 h:49.17±8.3 vs 28.64±6.4, P<0.01),percentage of released lactate dehydrogenase (LDH%)(4 h:26.9±6.1 vs 13.2±4.1; 8 h:31.4±4.9 vs 18.7±5.3; 16 h:47.7±6.5 vs 28.1±6.8, P<0.01) and neuron apoptosis(16 h: 42±7.8 vs 20.4±5.5, P<0.01). K (ATP) agonist Gli prevented the protective effects of Pin. Conclusion K (ATP) opener (Pinacidil) performs a neuroprotective role in anoxic/hypoglycemic injury which partly due to its suppression on neuron apoptosis.

关 键 词：吡那地尔 神经细胞缺氧缺糖损伤 ATP敏感性钾通道 缺氧缺糖损伤模型 细胞凋亡率 KATP开放剂 神经保护作用 正常对照组 乳酸脱氢酶 通道阻断剂 Pin 死亡率 大脑皮层 体外培养 格列苯脲 LDH 24h 再复氧 干预后 P值 

分 类 号：R965[医药卫生—药理学]