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目的探讨尼莫地平(nimodipin,NIM)对戊四氮(pentylenetetrazol,PTZ)点燃癫痫大鼠空间学习记忆能力及海马细胞内游离Ca2+浓度([Ca2+]i)、Ca2+/钙调蛋白依赖性蛋白激酶Ⅱα(calcium/calmodulin-dependent protein kinaseⅡα,CaMKⅡα)蛋白表达的影响。方法将动物分为正常对照组、PTZ组和NIM+PTZ组,采用PTZ慢性点燃癫痫模型,应用Mor-ris水迷宫观察各组大鼠空间学习记忆能力,运用流式细胞仪检测海马细胞内[Ca2+]i变化,Western blot方法测定CaMKⅡα蛋白的表达。结果PTZ组大鼠空间学习记忆能力受损,其海马细胞内[Ca2+]i明显升高(P<0.05),CaMKⅡα蛋白水平较正常对照组减少(P<0.05);与PTZ组比较,NIM+PTZ组大鼠空间学习记忆能力好转,其海马细胞内[Ca2+]i下降(P<0.05),CaMKⅡα蛋白水平升高(P<0.05)。结论PTZ点燃癫痫大鼠海马存在钙超载及CaMKⅡα的表达异常,由此引起大鼠空间学习记忆能力受损;NIM可以降低细胞内[Ca2+]i,提高CaMKⅡα的表达,改善癫痫大鼠的学习记忆能力。
Objective To investigate the effect of nimodipin (NIM) on the spatial learning and memory of hippocampal neurons in hippocampus of rats with pentylenetetrazol (PTZ) -induced epilepsy and the changes of intracellular free Ca2 + concentration ([Ca2 +] i), Ca2 + / calmodulin-dependent protein kinase Ⅱα (calcium / calmodulin-dependent protein kinase Ⅱ α, CaMKⅡα) protein expression. Methods The animals were divided into normal control group, PTZ group and NIM + PTZ group. PTZ chronic ignition epilepsy model was used. Morris water maze was used to observe spatial learning and memory ability of rats in each group. Flow cytometry was used to detect intracellular [ Ca2 +] i changes, Western blot determination of CaMKIIα protein expression. Results The spatial learning and memory abilities of rats in PTZ group were impaired, the [Ca2 +] i in hippocampus was significantly increased (P <0.05), and the level of CaMKIIα protein was decreased in normal rats (P <0.05). Compared with PTZ group, The spatial learning and memory capacity of PTZ group was improved, the [Ca2 +] i in hippocampus decreased (P <0.05), and the level of CaMKⅡa protein increased (P <0.05). Conclusion The calcium overload and the expression of CaMKⅡα in the hippocampus of PTZ-kindled epilepsy rats may be impaired, resulting in impaired spatial learning and memory ability. NIM can decrease the intracellular [Ca 2+] i, increase the expression of CaMKⅡα, and improve the learning and memory of epileptic rats ability.