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目的:观察钙敏感受体在癫痫大鼠心肌细胞中的表达和丝裂原活化蛋白激酶途径的变化。方法:戊四氮成功点燃慢性癫痫模型;Wistar健康雄性大鼠随机分为5组:对照组;癫痫组;癫痫+精胺组;癫痫+精胺+Chalhex231组;癫痫+Chalhex231组,每组各12只。模型组用PTZ亚惊厥剂量(35 mg/kg)持续腹腔注射28 d后停药1周,再用相同剂量的PTZ测试,对照组以等容生理盐水代替PTZ腹腔注射,依据Racine行为学分级标准出现连续5次出现Ⅱ级以上发作者视为成功点燃慢性癫痫模型;以钙敏感受体激动剂精胺,钙敏感受体抑制剂Chalhex231做为干预因素,(精胺3μmol/L和Chalhex231 2μmol/L);检测血清肌酸激酶、肌酸激酶同工酶;检测心肌功能、大鼠心肌组织形态学变化、心肌细胞的超微结构、心肌中钙敏感受体以及细胞外调节蛋白激酶ERK、p-ERK、p-JNK表达情况。结果:与正常组比较,癫痫组CK、CK-MB含量明显升高,心脏超声显示心脏顺应性下降,左室功能降低,E/A<1。心肌细胞超微结构显示损伤严重。CaSR表达进一步增加,p-JNK蛋白表达增加,p-ERK蛋白表达减少。精胺能够促进癫痫所诱发的CaSR蛋白表达增多、p-JNK蛋白表达增加,p-ERK蛋白表达减少;Chalhex231的作用相反。结论:慢性癫痫可诱发心肌改变,CaSR表达增多可能参与癫痫慢性发作时心肌损伤,MAPK信号通路可能参与慢性癫痫心肌损伤过程。
OBJECTIVE: To observe the expression of calcium-sensitive receptors in cardiomyocytes of epileptic rats and the changes of mitogen-activated protein kinase pathway. METHODS: Pentylenetetrazole was used to ignite chronic epilepsy model. Wistar healthy male rats were randomly divided into 5 groups: control group, epilepsy group, epilepsy + spermine group, epilepsy + spermine + Chalhex231 group, epilepsy + Chalhex231 group 12 only. The rats in model group were treated with PTZ subacute dose (35 mg / kg) for 28 days and then discontinued for 1 week. The rats in the control group were given the same dose of PTZ. The rats in the control group were given isocrinal saline instead of PTZ intraperitoneally. According to Racine’s behavioral grading standards The patients with grade Ⅱ or higher appeared for 5 consecutive times as the successful ignition of chronic epilepsy model. The calcium sensitive receptor agonist spermine and calcium sensitive receptor inhibitor Chalhex231 were taken as the intervention factors (spermine 3μmol / L and Chalhex231 2μmol / L). Serum creatine kinase and creatine kinase isoenzymes were detected. Cardiac function, cardiac morphological changes in rat myocardium, myocardial ultrastructure, calcium-sensitive receptors in myocardium and extracellular regulated protein kinase ERK, p -ERK, p-JNK expression. Results: The levels of CK and CK-MB in epilepsy group were significantly higher than those in normal group. Echocardiography showed decreased cardiac compliance and decreased left ventricular function with E / A <1. Myocardial ultrastructure showed severe damage. CaSR expression further increased, p-JNK protein expression increased, p-ERK protein expression decreased. Spermine can promote epilepsy induced CaSR protein expression increased p-JNK protein expression, p-ERK protein expression decreased; Chalhex231 the opposite effect. CONCLUSION: Chronic epilepsy can induce myocardial changes. The increased expression of CaSR may play a role in myocardial injury during chronic epilepsy. The MAPK signaling pathway may be involved in the process of myocardial damage in chronic epilepsy.