2型糖尿病(T2DM)是一种多病因的复杂代谢性疾病,涉及遗传和环境因素。随着现代生活的变化,工作压力等慢性心理压力源受到越来越多的关注。慢性心理应激可诱发或加重糖尿病,反过来,随着T2DM的恶化,患者经常经历不同程度的抑郁,焦虑,和其他负面情绪。为了阐明滋补养阴方(ZBPYR)在调节肝脏线粒体相关内质网膜蛋白质组改善T2DM伴慢性心理应激中的作用,在Zucker瘦肉同窝(对照组)中鉴定出差异表达蛋白(DEP),慢性心理应激T2DM大鼠(模型组),和ZBPYR给药大鼠(ZBPYR组)通过iTRAQ与LC-MS/MS。使用Mfuzz软聚类分析,DEP分为六个不同的集群。集群1-6包含5、68、44、57、28和32个DEP,分别。鉴于ZBPYR可减轻T2DM慢性心理压力时的症状并影响其探索行为,我们重点研究了模型:对照组和ZBPYR:模型组之间表达趋势相反的簇。我们筛选出第1、3和4组中的DEP,这些DEP可能是预防和治疗2型糖尿病伴慢性心理压力的良好候选者。并进一步进行了生物信息学分析。DEP主要参与胰岛素信号通路,氧化磷酸化,三羧酸循环,氨基酸代谢,溶酶体相关过程,和脂质代谢。这可能提示T2DM伴慢性心理应激的致病基础和ZBPYR的潜在治疗机制。此外,两种关键蛋白质,溶酶体相关蛋白(Lamp2)和三羧酸循环相关蛋白(Suclg1),可能代表具有慢性心理压力的T2DM的新型生物标志物和ZBPYR的药物靶标。Western印迹分析还显示这两种蛋白质在模型和ZBPYR组的肝MAMs中的相似表达模式。
Type 2 diabetes mellitus (T2DM) is a complex metabolic disease with multiple etiologies, involving both genetic and environmental factors. With changes associated with modern life, increasing attention has been paid to chronic psychological stressors such as work stress. Chronic psychological stress can induce or aggravate diabetes mellitus, and conversely, with the deterioration of T2DM, patients often experience different degrees of depression, anxiety, and other negative emotions. In order to clarify the role of ZiBuPiYin recipe (ZBPYR) in regulating the liver mitochondria-associated endoplasmic reticulum membrane proteome to improve T2DM with chronic psychological stress, differentially expressed proteins (DEPs) were identified among Zucker lean littermates (control group), chronic psychological stress T2DM rats (model group), and ZBPYR administration rats (ZBPYR group) through iTRAQ with LC-MS/MS. Using Mfuzz soft clustering analysis, DEPs were divided into six different clusters. Clusters 1-6 contained 5, 68, 44, 57, 28, and 32 DEPs, respectively. Given that ZBPYR can alleviate T2DM symptoms and affect exploratory behavior during T2DM with chronic psychological stress, we focused on the clusters with opposite expression trends between model:control and ZBPYR:model groups. We screened out the DEPs in clusters 1, 3, and 4, which may be good candidates for the prevention and treatment of T2DM with chronic psychological stress, and further conducted bioinformatics analyses. DEPs were mainly involved in the insulin signaling pathway, oxidative phosphorylation, tricarboxylic acid cycle, amino acid metabolism, lysosome-related processes, and lipid metabolism. This may indicate the pathogenic basis of T2DM with chronic psychological stress and the potential therapeutic mechanism of ZBPYR. In addition, two key proteins, lysosome-associated protein (Lamp2) and tricarboxylic acid cycle-related protein (Suclg1), may represent novel biomarkers for T2DM with chronic psychological stress and drug targets of ZBPYR. Western blot analyses also showed similar expression patterns of these two proteins in liver MAMs of the model and ZBPYR groups.