高同型半胱氨酸血症小鼠额叶皮质神经元损伤及其Hes1/Notch1表达的初步研究  

Neuron injury of frontal cortex and the expression of Hes1/Notch1 in mice with hyperhomocysteinemia

作　　者：龙乾 许贤瑞[2] 燕茹 刘峰 张特弟 张竞文[1] LONG Qian;XU Xianrui;YAN Ru;LIU Feng;ZHANG Tedi;ZHANG Jingwen(School of Basic Medicine,Ningxia Medical University,Yinchuan 750004,China;Department of Neurology,General Hospital of Ningxia Medical University,Yinchuan 750004,China;Department of Cordid Lenter,General Hospital of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学基础医学院,宁夏银川750004 [2]宁夏医科大学总医院神经内科,宁夏银川750004 [3]宁夏医科大学总医院心脏中心,宁夏银川750004

出　　处：《宁夏医学杂志》2021年第2期102-104,共3页Ningxia Medical Journal

基　　金：宁夏医科大学2018年自治区级“大学生创新创业计划项目”;宁夏医科大学优秀青年后备骨干培养项目(2018年);宁夏医科大学校级科研基金项目(2019002)。

摘　　要：目的探讨高同型半胱氨酸血症神经细胞损伤及其可能机制。方法将ApoE^(-/-)小鼠分为高同型半胱氨酸血症实验组(HM)和ApoE^(-/-)小鼠对照组(ApoE^(-/-)),每组12只;ApoE野生型c57/6J小鼠为空白对照组(Con)。HM组小鼠采用高蛋氨酸饮食饲喂造成高同型半胱氨酸血症,Con组和ApoE^(-/-)组小鼠普通饮食饲喂。通过组织病理学、组织化学、TUNEL染色观察小鼠额叶皮质神经元变化,qPCR检测脑组织Hes1、Notch1表达。结果 HM组小鼠血浆总同型半胱氨酸为(18.87±6.79)μmoL/L,明显高于Con组和ApoE^(-/-)组(P<0.05);HE染色可见,HM组固缩神经元有所增加。经光密度测定可见,3组Nissl体平均光密度值差异无统计学意义(P>0.05)。TUNEL染色可见,Con组和ApoE^(-/-)组小鼠均偶见TUNEL阳性神经元,HM组中TUNEL阳性神经元比例明显增加(P<0.05);通过qPCR可见,HM组Hes1和Notch1基因mRNA表达明显高于Con组和ApoE^(-/-)组(P<0.05)。结论高同型半胱氨酸血症能够诱导额叶皮质神经元凋亡,可能涉及Hes1和Notch1表达的变化。Objective To investigate the characteristics of neuronal cells damage in hyperhomocysteine(HHcy)and its possible mechanism.Methods ApoE^(-/-)mice were divided into hyperhomocysteine experimental group(HM),control group of ApoE^(-/-)mouse(ApoE^(-/-)and blank control group of ApoE wild-type C57/6J mice(CON).Hyperhomocysteinemia was induced by a high-methionine diet in HM group.Mice in CON group and ApoE^(-/-)group were fed with normal diet.The changes of frontal cortex neurons were observed by histopathology,histochemistry and TUNEL staining,and the expression of Hes1 and Notch1 in frontal cortex were detected by qPCR.Results The total plasma homocysteine in HM group[(18.87±6.79)μmol/L]was significantly higher than that in CON group[(6.15±2.31)μmol/L]and ApoE^(-/-)group[(10.15±3.03)μmol/L](P<0.05).Histopathological examination showed that there was an increase of pyknosis neurons in HM group.According to the Nissl body staining showed that there was no significant difference in the average optical density of Nissl bodies in the three groups(P>0.05).The numbers of TUNEL positive neurons were occasionally seen in both CON group and ApoE^(-/-)group,and the proportion of TUNEL positive neurons was significantly increased in HM group(P<0.05).The expression of Hes1mRNA and Notch1mRNA in HM group was significantly higher than that in CON group and ApoE^(-/-)group(P<0.05).Conclusion Hyperhomocysteinemia can induce the apoptosis of frontal cortex neurons,which may be involved in the expression changes of Hes1 and Notch1.

关 键 词：高同型半胱氨酸血症 神经元 凋亡 

分 类 号：R740.3[医药卫生—神经病学与精神病学]