| 熊伯成,黎上明,但丁,邹良玉,杨细飞.肌萎缩侧索硬化症模型小鼠脑干蛋白质组学分析.[J].中南医学科学杂志.,2023,(5):630-634. |
| 肌萎缩侧索硬化症模型小鼠脑干蛋白质组学分析 |
| Proteomic analysis of brainstem in a mouse model of amyotrophic lateral sclerosis |
| 投稿时间：2023-05-08 修订日期：2023-08-12 |
| DOI：10.15972/j.cnki.43-1509/r.2023.05.002 |
| 中文关键词: 肌萎缩侧索硬化症 脑干 蛋白质组学 炎症 [ |
| 英文关键词:amyotrophic lateral sclerosis brainstem proteomics inflammation |
| 基金项目:国家自然科学基金项目(82171583)；深圳市科技创新委员会重点基础研究计划项目(JCYJ20200109150717745XY、JCYJ20200109144418639)；深圳香港脑科学研究所-深圳基础研究项目(NYKFKT20190019)；深圳市医学重点学科建设经费资助(SZXK069)；深圳市医疗卫生三名工程项目(SZSM201611090) |
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| 中文摘要: |
| 目的研究肌萎缩侧索硬化症(ALS)模型小鼠脑干蛋白谱表达情况及其发病机制。 方法采用18周龄携带人类SOD1基因突变体的ALS模型(SOD1G93A)雌鼠(模型组)和野生型雌鼠(对照组)为研究对象。采用抓力测试评估小鼠四肢肌肉力量；悬挂测试和转棒测试评估小鼠的抓取力、耐力、平衡能力；爬竿测试和步态测试评估小鼠运动能力和协调能力。麻醉后取脑干组织用TMT标记,蛋白质组学分析两组差异表达蛋白,并进行GO与KEGG富集分析。 结果与对照组小鼠比较,ALS小鼠四肢肌肉力量、抓取力、耐力和平衡能力、运动能力和协调能力下降。脑干蛋白质组学共鉴定和量化了6 702种蛋白质,筛选出差异表达蛋白423个,其中上调蛋白265个,下调蛋白158个。 DAVID基因本体论分析结果显示,ALS小鼠脑干中蛋白富集于胶原蛋白纤维组织、细胞黏附蛋白、线粒体、细胞死亡的负调控等,KEGG 通路主要富集于EMC-受体相互作用、MAPK 信号通路等。 结论ALS小鼠脑干中炎症相关蛋白上调,线粒体相关蛋白和凋亡相关蛋白下调,提示多种机制参与了ALS疾病的发生发展。 |
| 英文摘要: |
| AimTo study the expression profile of brainstem proteins in a mouse model of Amyotrophic Lateral Sclerosis (ALS) and elucidate its pathogenic mechanisms. MethodsFemale mice carrying the human SOD1 gene mutation (SOD1G93A) and non-transgenic littermates (18 weeks of age) were used. Grip strength test was used to assess muscle strength of the mice's limbs; hanging wire test and rotarod test were used to evaluate their endurance and balance ability; pole test and gait analysis were used to evaluate their motor and coordination ability. After anesthesia, brain stem tissue was taken and labeled with TMT. Proteomics analysis was performed to analyze the differentially expressed proteins between the two groups, and GO and KEGG enrichment analysis was performed. ResultsCompared with the control group mice, ALS mice showed a decrease in limb muscle strength, grip power, endurance and balance ability, motor ability, and coordination ability (P＜0.05). 6 702 proteins in brainstem were identified and quantified by proteomics, and 423 differentially expressed proteins were screened, including 265 up-regulated proteins and 158 down-regulated proteins.DAVID gene ontology analysis showed that the proteins in the brainstem of ALS mice were enriched in collagen fiber organization, cell adhesion proteins, mitochondria, and negative regulation of cell death, etc. The KEGG pathway was mainly enriched in the EMC-receptor interactions and MAPK signaling pathway. ConclusionThe protein expression profile in the brainstem of the model mice underwent significant changes:inflammation-related proteins were upregulated, while mitochondria-related proteins and apoptosis-related proteins were downregulated. This suggests that multiple mechanisms are involved in the occurrence and progression of ALS in the mouse model. |
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