赣南医科大学学报2024，Vol.44Issue(11)：1093-1099,7.DOI:10.3969/j.issn.1001-5779.2024.11.001
GSS抑制线粒体自噬减轻慢性脑缺血大鼠神经元损伤的研究
GSS attenuating neuronal damage in rats with chronic cerebral ischaemia by inhibiting mitochondrial autophagy
摘要
Abstract
Objective:To investigate the protective effects of genisteinsodium sulfonate(GSS)on neurons and the possible mechanisms,and to provide a potential target for the treatment of chronic cerebral ischemia.Methods:A rat model of chronic cerebral ischemia was set up by modified bilateral common carotid artery occlusion(2-VO).The rats were divided into Sham group,2-VO+Vehicle group,and 2-VO+GSS group(1 mg·kg-1 GSS).After eight week,the brain tissues were taken from the rats.And the differentially expressed proteins in the brain tissues of rats in each group were identified by iTRAQ,and the differentially expressed proteins were subjected to GO annotation enrichment analysis and MCODE analysis.Meanwhile,the GEO database was searched with the keywords"brain injury"+"mitochondrial autophagy"to obtain the dataset for the bioconcentration pathway analysis.Subsequently,the mRNA and/or protein expression levels of HIF-1α,CypD and LC3Ⅱ/Ⅰ in the brain tissues of rats were detected by qPCR and Western blot(WB).Results:The results of proteomic determination and analysis suggested that GSS improved mitochondrial functions in brain tissue of 2-VO rats,including improving mitochondrial ATP synthesis,electron transport chain,oxidative phosphorylation procedure,cytochrome complex,respiratory chain complex,inner mitochondrial membrane organelle generation,etc.The result of the bioconcentration pathway analysis showed that mitochondrial autophagy was involved in the process of ischemia,aging and neuronal damage,among which the binding process of proteins or enzymes was the most significant.The result of qPCR and WB showed that GSS could markedly down-regulate the expression levels of mitochondrial CypD and LC3Ⅱ/Ⅰ,and the mRNA and protein expression levels of HIF-1α in brain tissues.Conclusion:The protective effect of GSS on neurons after chronic cerebral ischemia may be achieved by inhibiting mitochondrial excessive autophagy and thereby attenuating oxidative stress damage.关键词
慢性脑缺血/染料木素磺酸钠/线粒体自噬/缺氧诱导因子-1αKey words
Chronic cerebral ischemia/Genisteinsodium sulfonate/Mitochondrial autophagy/Hypoxia-inducible factor-1α分类
医药卫生引用本文复制引用
范梦瑶,邢亚康,袁志栋,罗维,陈琦晖,莫亦,黄志华,肖海,黎晓..GSS抑制线粒体自噬减轻慢性脑缺血大鼠神经元损伤的研究[J].赣南医科大学学报,2024,44(11):1093-1099,7.基金项目
国家自然科学基金项目(31760290,82160688) （31760290,82160688）
江西省自然科学基金项目(20202BABL206058) （20202BABL206058）
赣州市指导性科技计划项目(2022B-SF9554) （2022B-SF9554）
赣南医学院本科生科技创新项目(NO.10) （NO.10）
赣南医学院神经生物研究创新团队项目(TD2021JC06) （TD2021JC06）
