高同型半胱氨酸血症对ApoE^(-/-)小鼠脑组织的损伤  

hyperhomocysteinemia induced brain tissue injury in ApoE^(-/-)

在线阅读下载全文

作  者:张竞文[1] 燕茹 马艳梅[1] 杨兰 米晓娟 田英 丛广志 ZHANG Jingwen;YAN Ru;MA Yanmei;YANG Lan;MI Xiaojuan;TIAN Ying;CONG Guangzhi(School of Basic Medical Science,NHC Key Laboratory of Metabolic Cardiovascular Diseases Research,Ningxia Medical University,Yinchuan 750004,China;The Heart Center of General Hospital,Ningxia Medical University,Yinchuan 750004,China)

机构地区:[1]宁夏医科大学基础医学院国家卫生健康委员会代谢性心血管疾病研究重点实验室,银川750004 [2]宁夏医科大学总医院心脏中心,银川750004

出  处:《神经解剖学杂志》2023年第5期537-544,共8页Chinese Journal of Neuroanatomy

基  金:宁夏回族自治区重点研发计划(2019BEG03006);宁夏回族自治区自然科学基金(2022AAC03192);宁夏医科大学科学研究基金(XT2020014)。

摘  要:目的:探讨高同型半胱氨酸血症(HHcy)对小鼠神经损伤的病理学基础。方法:ApoE^(-/-)小鼠分为对照组(control)、HHcy组(HHcy)和HHcy、叶酸及维生素B12干预组(MFB)。通过高蛋氨酸饮食诱发HHcy小鼠模型,采用组织学、组织化学、电子显微镜等观察小鼠脑组织结构和神经细胞超微结构变化,免疫组化染色观察nestin和一氧化氮合酶(NOS)表达。结果:高蛋氨酸饮食导致ApoE^(-/-)小鼠血浆同型半胱氨酸水平显著升高,脑组织基本结构未见明显异常,对照组、HHcy组和MFB组之间尼氏体平均光密度值无显著性差异。免疫组化染色可见,对照组、HHcy组和MFB组脑微血管分布均匀,未见明显差异。超微结构可见,HHcy组脑毛细血管内皮细胞出现多个微绒毛样突起;HHcy组神经元自噬体及空泡化线粒体显著多于对照组和HHcy组(P<0.05)。HHcy组和MFB组TUNEL阳性细胞比例明显多于对照组(P<0.05)。免疫组化可见,HHcy组室管膜下区nestin阳性细胞比例明显低于对照组(P<0.05),MFB组与对照组及HHcy组之间nestin阳性细胞比例无显著差异;与对照组相比,HHcy组和MFB组额叶皮质nNOS阳性细胞比例明显降低(P<0.05),iNOS阳性细胞比例显著升高(P<0.05)。结论:高同型半胱氨酸可诱导小鼠神经细胞氧化应激、自噬和凋亡增加、室管膜下区神经干细胞储备减少。Objective:To explore the pathology of neurological disfunction induced by hyperhomocysteinemia(HHcy).Methods:ApoE^(-/-)mice were divided into control group(control),HHcy group(HHcy),and HHcy,folic acid and vitamin B12 intervention group(MFB).HHcy was induced by high methionine diet.Histology,histochemistry,electron microscope and immunohistochemistry were used to comparatively observe the structural and ultrastructural changes of brain tissue and neuronal cells.The expression of nestin and nitric oxide synthase(NOS)was detected by immunohistochemistry staining.Results:HHcy was induced by high methionine diet in mice,and there was no obvious abnormality in the essential histology of brain.There was no significant difference in the mean optical density of Nissl body among the control,HHcy and MFB groups.As shown in CD31 immunohistochemistry,the microvessels in brain tissue of each group were evenly distributed.Ultrastructure showed that there were many microvilli-like processes in endothelial cells of capillary in HHcy group.In HHcy group,there were more autophagosomes and mitochondria vacuolation.Compared with control group,autophagosomes and mitochondria vacuolation in HHcy group were significantly increased(P<0.05).The proportion of TUNEL positive cells in HHcy group and MFB group was significantly higher than that in control group(P<0.05).The cells nestin-labeled in the subependymal region of HHcy group were significantly less than that in control group(P<0.05).There was no significant difference in the proportion of nestin-labeled cells between MFB group and control and HHcy groups.Immunohistochemistry showed that nNOS-labeled cells in the frontal cortex of HHcy and MFB groups decreased significantly,and the iNOS-labeled cells in HHcy group increased significantly compared with control group(P<0.05).Conclusion:Hyperhomocysteinemia might induce oxidative stress,autophagy and apoptosis of neuronal cells,accompanied by a decreased stem cell reserve in the subependymal region.

关 键 词:自噬 凋亡 神经细胞 高同型半胱氨酸血症 超微结构 小鼠 

分 类 号:R589[医药卫生—内分泌] R741[医药卫生—内科学]

 

参考文献:

正在载入数据...

 

二级参考文献:

正在载入数据...

 

耦合文献:

正在载入数据...

 

引证文献:

正在载入数据...

 

二级引证文献:

正在载入数据...

 

同被引文献:

正在载入数据...

 

相关期刊文献:

正在载入数据...

相关的主题
相关的作者对象
相关的机构对象