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基于PCPA大鼠下丘脑蛋白互作网络分析挖掘失眠发病的分子机制

Molecular Mechanisms of Insomnia Revealed by Hypothalamic Protein Interaction Network Analysis in PCPA Rat Models
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摘要 目的采用蛋白质组学技术对PCPA失眠大鼠模型下丘脑蛋白质表达差异进行分析,探讨失眠模型大鼠在失眠过程中下丘脑的差异蛋白互作网络关系。方法将SD大鼠随机分为空白组、模型A组、模型B组,除空白组外全都给予PCPA造模,模型A组造模成功后立即取下丘脑,空白组与模型B组饲养7 d,待PCPA药效减退后取下丘脑。运用蛋白质组学技术检测各组大鼠下丘脑蛋白差异,以差异表达量上调或下调超过1.5倍作为变化阈值,筛选差异蛋白并分析其互作用关系。结果戊巴比妥钠翻正反射试验显示,模型A组、模型B组与空白组的大鼠睡眠潜伏期时间比较,潜睡眠时间均延长(P<0.01),睡眠持续时间均缩短(P<0.01);自发活动试验显示造模后模型A组、模型B组与空白组比较,自发举爪次数均增加(P<0.05)。根据蛋白互作关系网络分析,模型A组与空白组之间蛋白网络中有16个蛋白有较重要作用,其中Map1(T-kininogen 1)、Mfge8(Lactadherin)、P4hb(Protein disulfide-isomerase)与失眠关系较为密切。模型B组与模型A组之间蛋白网络中有12个蛋白具有重要作用,其中Apoa1(Apolipoprotein A-I)、Mfge8(Lactadherin)、Sympk(Symplekin)、Plg(Plasminogen)与失眠关系密切。结论通过PCPA大鼠下丘脑的蛋白互作网络分析挖掘,失眠的发生发展可能与HPA轴的应激反应下神经变性保护、血管内皮细胞、内分泌调节、免疫系统平衡、学习记忆能力以及衰老具有相关性。 Objective:To analyze the differential protein expression in the hypothalamus of PCPA-induced insomnia rat models using proteomics,and to explore the protein interaction networks involved in the pathogenesis of insomnia.Methods:SD rats were randomly divided into blank group,Model A group,and Model B group.Except for the blank group,all groups were modeled with PCPA.In the Model A group,the hypothalamus was harvested immediately after successful modeling,while in the blank and Model B groups,the hypothalamus was harvested after 7 days,allowing PCPA effects to subside.Proteomics technology was used to detect differential protein expression in the hypothalamus of each group.Proteins with differential expression levels greater than 1.5-fold(upregulated or downregulated)were identified and analyzed for interaction relationships.Results:Sodium pentobarbital righting reflex tests showed that sleep latency was significantly prolonged(P<0.01)and sleep duration significantly shortened(P<0.01)in both Model A and Model B groups compared to the blank group.Spontaneous activity tests revealed an increased number of paw lifts in the Model A and Model B groups compared to the blank group(P<0.05).Protein interaction network analysis identified 16 key proteins in the network between the Model A and blank groups,among which Map1(T-kininogen 1),Mfge8(Lactadherin),and P4hb(Protein disulfide-isomerase)were closely related to insomnia.In the network between the Model B and Model A groups,12 key proteins were identified,including Apoa1(Apolipoprotein A-I),Mfge8(Lactadherin),Sympk(Symplekin),and Plg(Plasminogen),which were strongly associated with insomnia.Conclusion:Protein interaction network analysis of the hypothalamus in PCPA-induced rat models suggests that the occurrence and progression of insomnia may be related to stress responses of the HPA axis,neurodegenerative protection,vascular endothelial cells,endocrine regulation,immune system balance,learning and memory abilities,and aging.
作者 张红石 曲子涵 矫俊东 张野 ZHANG Hong-shi;QU Zi-han;JIAO Jun-dong;ZHANG Ye(Changchun University of Traditional Chinese Medicine,Changchun 130117,China;The Affiliated Hospital of Changchun University of Traditional Chinese Medicine,Changchun 130021,China)
出处 《云南中医中药杂志》 2024年第12期82-87,共6页 Yunnan Journal of Traditional Chinese Medicine and Materia Medica
基金 国家自然科学基金面上项目(82074569) 吉林省自然科学基金项目(YDZJ202301ZYTS109)。
关键词 失眠 PCPA模型 下丘脑 蛋白质组学 蛋白互作关系 差异蛋白 Insomnia PCPA Model Hypothalamus Proteomics Protein Interaction Network Differential Proteins
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