基于蛋白质组学的时相性偏头痛大鼠模型不同时间点分子机制研究  

Molecular Mechanism of Migraine with Phasic Characteristics Model Rats at Different Time Points Based on Proteomic Analysis

作　　者：姚钰宁 韩赵成 曹光昭 樊欢欢 曹克刚[1,5] YAO Yuning;HAN Zhaocheng;CAO Guangzhao;FAN Huanhuan;CAO Kegang(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100007,China;Henan University of Chinese Medicine,Zhengzhou 450046,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100091,China;Shunyi Hospital,Beijing Traditional Chinese Medicine Hospital,Beijing 101300,China;Institute for Brain Disorders,Beijing University of Chinese Medicine,Beijing 100027,China)

机构地区：[1]北京中医药大学东直门医院,北京100007 [2]河南中医药大学,郑州450046 [3]中国中医科学院中药研究所,北京100091 [4]北京中医医院顺义医院,北京101300 [5]北京中医药大学中医脑病研究院,北京100027

出　　处：《世界中医药》2023年第13期1800-1807,1813,共9页World Chinese Medicine

基　　金：2022年青年岐黄学者培养项目(国中医药人教函[2022]256号)。

摘　　要：目的:筛选时相性偏头痛大鼠模型不同时间点下三叉神经节中差异蛋白,分析相关生物学过程,探索时相性偏头痛模型大鼠在不同时间点生物学过程的变化规律。方法:采用皮下注射多巴胺、硝酸甘油方法制备时相性偏头痛模型大鼠,在造模过程的不同时间点(注射多巴胺后11 min、22 min、33 min及注射硝酸甘油后1 h、2 h取大鼠三叉神经节,进行串联质谱标签(TMT)定量蛋白质组学测序,筛选不同时间点差异蛋白,并对差异表达蛋白进行基因本体(GO)功能注释富集分析。结果:与空白对照组比较,DA-11组有1323个差异蛋白,DA-22组有1392个差异蛋白,主要与氧化应激反应、代谢过程等生物学过程相关;DA-33组有961个差异蛋白,主要与氧化应激反应等生物学过程相关;GTN-1组有1051个差异蛋白,主要与炎症反应、凋亡等生物学过程相关;GTN-2组有1102个差异蛋白,主要与代谢过程等生物学过程相关。收缩相关键生物学过程主要为氧化应激反应、ATP代谢过程,舒张相关键生物学过程主要为TRP通道的炎症介质调节、细胞黏附。结论:时相性偏头痛大鼠模型在不同时间点的分子机制生物学过程具有动态变化的特点,收缩相以氧化应激状态为主,而舒张相以炎症反应、TRP通道的激活为主。以上特点能够为后续偏头痛动态变化病理机制与基于时相精准治疗奠定基础。Objective:To screen differential proteins in the trigeminal ganglia of migraine rats with phasic characteristics at different time points,analyze the related biological processes,and explore the changes in biological processes at different time points in the migraine with phasic characteristics rat model.Methods:The migraine with phasic characteristics model was established in rats by subcutaneous injection of dopamine and nitroglycerin.At different time points during the modeling process(11 min,22 min,and 33 min after dopamine injection;1 h and 2 h after nitroglycerin injection),the trigeminal ganglia were collected from the rats.Tandem mass tag(TMT)quantitative proteomics sequencing was performed to screen differential proteins at different time points,and the differentially expressed proteins were subjected to Gene Ontology(GO)functional annotation and enrichment analysis.Results:Compared with the blank control group,there were 1323 differential proteins in the DA-11 group and 1392 differential proteins in the DA-22 group,primarily related to biological processes such as oxidative stress response and metabolic processes.The DA-33 group had 961 differential proteins,primarily related to oxidative stress response and other biological processes.The GTN-1 group had 1051 differential proteins,mainly associated with biological processes such as inflammation response and apoptosis.The GTN-2 group had 1102 differential proteins,primarily related to metabolic processes.Key biological processes associated with contraction were mainly oxidative stress response and ATP metabolism,while key biological processes associated with relaxation were inflammation mediator regulation of TRP channels and cell adhesion.Conclusion:The molecular mechanism and biological processes in the rat model of migraine with phasic characteristics exhibit dynamic changes at different time points.The contraction phase is characterized by oxidative stress,while the relaxation phase is characterized by inflammation response and activation of TRP chan

关 键 词：蛋白质组学 偏头痛 时相性 分子机制 大鼠模型 差异蛋白 生物学过程 三叉神经节 

分 类 号：R277.7[医药卫生—中医学] R741