目的 观察戊四氮(pentetrazole,PTZ )点燃急性癫痫大鼠模型心肌中钙敏感受体(calcium sensing receptor,CaSR)表达及磷脂酰肌醇3-激酶/蛋白激酶B(Phosphatidylinositol3-kinase/protein kinase B,Pi3k/Akt)通路在调节心肌细胞凋亡过程中的变化。方法 Wistar大鼠随机分为正常对照组和癫痫组。采用腹腔注射PTZ(64 mg/kg)1 次,建立急性癫痫大鼠模型。脑电图检测大脑异常改变。心脏彩超检测心率、左心室缩短分数和左心室射血分数。检测血清肌酸激酶(creatine kinase,CK)、血清肌酸激酶同工酶(creatine kinase-MB,CK-MB)和肌钙蛋白(cardiac troponin-I,cTnI)。分别在光镜和电镜下观察心肌细胞形态学和超微结构变化。Western blotting分别观察心肌CaSR、Akt和磷酸化蛋白激酶B(phosphorylation-protein kinase B ,p-Akt)蛋白表达。结果 癫痫组脑电图检查提示大脑出现异常放电;心脏彩超见癫痫组心率增快,M型曲线显示左室壁节律失调,左心室缩短分数癫痫组值降低;左心室射血分数癫痫组值降低。血清酶CK、CK-MB、cTnI较正常组增高,差异具有统计学意义(P<0.05)。镜下显示癫痫组心肌细胞结构损伤明显;癫痫组CaSR、 p-Akt表达升高,差异具有统计学意义(P<0.05),Akt两组表达无明显差别。结论 癫痫可致心肌损伤,引起心肌细胞中CaSR表达增加,激活心肌细胞抗凋亡Pi3k/Akt通路,促使p-Akt表达上调,共同调节心肌细胞凋亡。

Objectives To observe the changes of the expression of calcium-sensing receptor and Pi3k/Akt pathway in regulating cardiac myocyte apoptosis of epilepsy rat. Methods Adult male Wistar rats were divided into two groups randomly:normal control group and epilepsy group.The epilepsy rats group model were induced by subcutaneous injection of PTZ (64 mg/kg once).The level of CK,CK-MB and cTnI were assayed by ultraviolet spectrophotometry.The morphological changes of cardiac tissues were observed under optical and electron microscopy.Heart rate and the cardiac function of the rats in each group were detected by echocardiography.The expressions of CaSR,Akt and p-Akt were analyzed by western blot. Results Compared with control group,CK,CK-MB and cTnI were increased obviously in epilepsy group (P<0.05).HE staining showed the cell swelled,and the nuclear fragmented.EEG showed epilepsy waves.By echocardiography,rhythm of the heart was increased,the left ventricular wall motion was abnormal,and the rhythm was disorder.The expression of CaSR,p-Akt were increased in epilepsy group(P<0.05),while Akt had no difference between of them. Conclusion Epileptic may injured cardiac tissues,and induced the increased expression of CaSR,and actived Pi3k/Akt pathway,then increased the expression of p-Akt,all of them regulated the cardiac myocyte apoptosis.