【摘要】 目的 探讨钙离子通道在缺氧缺糖/再灌注诱导皮质神经元损伤中的作用。方法 采用培养的大鼠皮质神经元缺氧缺糖模型,应用DAPI染色方法,以细胞凋亡率为指标,观察缺氧缺糖诱导神经元损伤及Ca²⁺螯合剂EGTA、NMDA受体拮抗剂MK-801、L-型电压门控钙通道（L-VGCC）拮抗剂尼莫地平、蛋白酪氨酸激酶（PTK）抑制剂染料木黄酮、CaMKⅡ抑制剂NK-62对缺氧缺糖/再灌注诱导神经元损伤的作用。结果 缺氧缺糖/再灌注诱导细胞发生凋亡,至再灌注24 h凋亡率达到80%左右;加入EGTA、MK-801及尼莫地平可以抑制细胞凋亡,凋亡率从80%分别降低为33%、35%和38%;加入染料木黄酮和KN-62可以使凋亡率从80%分别降低为43%和42%。结论 减少胞外Ca²⁺浓度、阻断NMDA受体和L-VGCC、抑制蛋白酪氨酸激酶和CaMKⅡ可以减少缺氧缺糖/再灌注诱导的神经元损伤。缺氧缺糖/再灌注诱导的神经元损伤可能与胞外Ca²⁺内流有关,并与NMDA受体和L-VGCC两类钙通道的开放有关。更多还原

【Abstract】 Objective To study the roles of calcium channels in cultured cortical neuronal injury induced by oxygen-glucose deprivation（OGD）.Methods We investigated the apoptosis of cultured cortical neurons induced by OGD and reoxygen.We also evaluated the effects of EGTA(the eliminator of extracellular Ca²⁺),MK-801（a selective antagonist of NMDA receptor）,nimodipine（the blocker of L-type voltage-gated calcium channel,L-VGCC）,genistein（the inhibitor of PTK） and KN-62（the inhibitor of CaMK Ⅱ） on the delayed neuronal death in cultured cortical neurons.Results The apoptosis of cultured cortical neurons was induced by OGD and reoxygen.Then the apoptotic rates peaked at 80% at 24 h of reoxygen.The apoptotic rates were decreased by EGTA,MK-801 and nimodipine from80% to 33%,35% and 38%,respectively.While genistein and KN-62 decreased the proportion of apoptotic cells from 80% to 43% and 42%.Conclusion The eliminator of extracellular Ca²⁺,the blocker of NMDA receptor and LVGCC,the inhibitor of PTK and CaMK Ⅱ may decrease the apoptosis-like cell death induced by OGD.These results suggest that apoptosis of cortical neurons induced by OGD and reoxygen may be associated with the extracelluar Ca²⁺ influx and the openness of NMDA receptor and L-VGCC.更多还原