miR34a在戊四氮致癫痫大鼠中通过下调Bcl-2导致神经元凋亡  

MiR34a induces neuronal apoptosis by downregulating Bcl-2 in rats with epilepsy induced by PTZ

作　　者：金绍静[1] 马巍 张淑红[1] 金岳雷[1] 刘东海 王淑秋[1] 朱金玲[1] JIN Shaojing;MA Wei;ZHANG Shuhong(School of Basic Medicine,Jiamusi University,Jiamusi 154007,China)

机构地区：[1]佳木斯大学基础医学院,黑龙江佳木斯154007

出　　处：《中风与神经疾病杂志》2018年第7期617-621,共5页Journal of Apoplexy and Nervous Diseases

基　　金：黑龙江省教育厅高校基本科研业务费立项(No.2017-KYYWF-0583);佳木斯大学创新团队项目(No.CXTDPY-201602)

摘　　要：目的探讨miR34a对戊四氮致癫痫大鼠的影响及其可能的机制。方法将24只雄性健康的Wister大鼠随机分为正常对照组和癫痫组(PTZ 35 mg/kg),采用腹腔注射方式,连续注射28 d最后一次施用药物24 h后处死实验大鼠、取材。通过Racine评分标准对癫痫大鼠模型的建立进行评价;应用生物信息学方法分析癫痫大鼠海马中差异表达的、靶向Bcl-2的miRNA;应用qRT-PCR方法验证检测大鼠海马中miRNA34a的表达情况;应用Western blot检测大鼠海马中bcl-2的表达情况;应用Hoechst检测大鼠海马神经元的凋亡情况。结果癫痫组大鼠的Racine评分明显高于正常对照组(P<0.01);通过生物信息学方法发现miRNA34a是差异高表达前十的miRNA中唯一可以靶向Bcl-2的miRNA;癫痫组大鼠海马组织中miR34a的表达量明显高于正常对照组(P<0.01)、Bcl-2的表达量明显低于正常对照组(P<0.01)、海马神经元凋亡情况明显高于正常对照组(P<0.01)。结论miRNA34a对戊四氮致癫痫大鼠海马可能具有损伤神经元的作用,并且其作用机制可能是通过下调Bcl-2导致海马神经元凋亡进而对癫痫大鼠产生影响。Objective To investigate the effect of miR34a on pentylenetetrazole-induced epileptic rats and its possible mechanism. Methods Twenty-four male Wistar rats were randomly divided into normal control group and epilepsy group （PTZ 35 mg/kg）. Intraperitoneal injection was used for 28 consecutive days. The experimental rats were executed 24 hours after the last drug application. The rat model of epilepsy was evaluated by Racine scoring system;Bioinformatics methods were used to analyze the differentially expressed miRNAs and targeted Bcl-2 in hippocampus of epileptic rats;qRT-PCR method was used to verify the expression of miRNA34 in hippocampus of rats. The expression of bcl-2 in hippocampus of rats was detected by Western blot;Hoechst was used to detect the apoptosis of hippocampal neurons. Results Racine scores in epileptic rats were significantly higher than those in normal controls （P〈0.01）. The bioinformatics method to find that miRNA34a was the only miRNA to targeted Bcl-2.The expression of miR34a in hippocampus of epileptic rats was significantly higher than normal controls （P〈0.01）. The expression of Bcl-2 was significantly lower than the normal control group （P〈0.01）. The apoptosis of hippocampal neurons was significantly higher than the normal control group （P〈0.01）. Conclusion miRNA34a have impaired neurons of the hippocampus of epileptic rats,and its mechanism may be through the down-regulation of Bcl-2 leading to apoptosis of hippocampus neurons.

关 键 词：癫痫 miRNA34a BCL-2 细胞凋亡 

分 类 号：R742.1[医药卫生—神经病学与精神病学]