慢性癫痫大鼠心肌中钙敏感受体及丝裂原活性蛋白激酶表达的改变

doi:10.13459/j.cnki.cjap.2016.05.018

中国应用生理学杂志 ›› 2016, Vol. 32 ›› Issue (5): 454-458.doi: 10.13459/j.cnki.cjap.2016.05.018

慢性癫痫大鼠心肌中钙敏感受体及丝裂原活性蛋白激酶表达的改变

郭津¹, 刘阳^1,4, 王超², 白玲玲¹, 韩小唯², 张鑫阳¹, 孙艳秋¹, 王鲁川², 姜志梅^1,3

1. 佳木斯大学附属第三医院, 黑龙江佳木斯 154002;
2. 佳木斯大学附属第一医院, 黑龙江佳木斯 154002;
3. 哈尔滨医科大学公共卫生学院, 黑龙江哈尔滨 150026;
4. 哈尔滨市第四医院, 黑龙江哈尔滨 150026

收稿日期:2015-04-14 修回日期:2016-04-19 出版日期:2016-09-28 发布日期:2018-06-20
通讯作者: 姜志梅,Tel:13846163601;E-mail:mynard93@163.com E-mail:mynard93@163.com
基金资助:
国家自然科学基金资助项目（81300122）；黑龙江省青年科学基金项目（QC2016130）；佳木斯大学校级创新团队（Cxtd201302）

The expression of calcium sensing receptor(CaSR) and MAPK pathway changes in myocardial cells of epilepsy rats

GUO Jin¹, LIU Yang^1,4, WANG Chao², BAI Ling-ling¹, HAN Xiao-wei², ZHANG Xin-yang¹, SUN Yan-qiu¹, WANG Lu-chuan², JIANG Zhi-mei^1,3

1. The Affiliated the Third Hospital, Jiamusi 154002;
2. The Affiliated the First Hospital Jiamusi University, Jiamusi 154002;
3. Harebin MedicalCollege of Public Health, Harebin 150026, China;
4. Harebin NO.4 Hospital

Received:2015-04-14 Revised:2016-04-19 Online:2016-09-28 Published:2018-06-20
Supported by:
国家自然科学基金资助项目（81300122）；黑龙江省青年科学基金项目（QC2016130）；佳木斯大学校级创新团队（Cxtd201302）

摘要/Abstract

摘要： 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3 μmol/L和Chalhex231 2 μmol/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。

关键词: 钙敏感受体, 丝裂原活化蛋白激酶, 癫痫, 心肌, 大鼠

Abstract: Objective: To investigate the changes of the myocardial cells in chronic epileptic rat model and to observe the expression of calcium sensing receptor(CaSR) and mitogen-activated proteinkinase(MAPK)pathway changes in epilepsy rats. Methods: The chronic epileptic rat model was induced bypentetrazole (PTZ). Adult male Wistar rats were divided into 5 groups randomly, and there were 12 rats in each group. The rats in model group were treated with a sub-convulsivedose of PTZ (35 mg/kg) by intraperitoneal injection for 28 d. After stopping a week, the same dose of PTZ test was conducted. The control group was treated with isovolumetric saline instead of PTZ by intraperitoneal injection. According to Racine behavior grading standards the rat emerged two levels above epileptic seizure 5 consecutive times, which was considered the chronic epilepsy model successful ignition. The intervention factors included spermine(calcium-sensing receptor agonist, 3 μmol/L) and Chalhex231(calcium-sensing receptor inhibitor, 2 μmol/L). The serum creatine kinase (CK) and creatine kinase isoenzyme(CK-MB)were detected. The cardiac functions, morphological changes of rat myocardial tissue, myocardial cell ultrastructure, myocardial cell calcium sensing receptor and extracellular regulated protein kinase (ERK), p-ERK, p-JNK expression were carried out. Results: Compared with normal control group, CK, CK-MB inPTZ group were increased obviously. The cardiac compliance and left ventricular function were decreased, E/A<1 by echocardiography. The myocardial ultrastructure showed serious injury. The expressions of CaSR and p-JNK were increased, but the expression of p-ERKwas decreased. Spermine could promote the expressions of CaSR and p-JNK, and decrease the expression of p-ERK in epilepsy; however, the role of Chalhex231 wasopposite. Conclusion: The level of CaSR expression increased in chronic epileptic rat model. CaSR activated the expressions of MAPK of the myocardial cells,andthen influenced the cardiac myocyte apoptosis.

Key words: calcium-sensing receptor, mitogen-activated proteinkinase, epilepsy, myocardial cells

郭津, 刘阳, 王超, 白玲玲, 韩小唯, 张鑫阳, 孙艳秋, 王鲁川, 姜志梅. 慢性癫痫大鼠心肌中钙敏感受体及丝裂原活性蛋白激酶表达的改变[J]. 中国应用生理学杂志, 2016, 32(5): 454-458.

GUO Jin, LIU Yang, WANG Chao, BAI Ling-ling, HAN Xiao-wei, ZHANG Xin-yang, SUN Yan-qiu, WANG Lu-chuan, JIANG Zhi-mei. The expression of calcium sensing receptor(CaSR) and MAPK pathway changes in myocardial cells of epilepsy rats[J]. CJAP, 2016, 32(5): 454-458.

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慢性癫痫大鼠心肌中钙敏感受体及丝裂原活性蛋白激酶表达的改变

The expression of calcium sensing receptor(CaSR) and MAPK pathway changes in myocardial cells of epilepsy rats

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