College of Chinese Medicine, Medical School, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, China.
Eur Rev Med Pharmacol Sci. 2023 Apr;27(7):2908-2918. doi: 10.26355/eurrev_202304_31922.
The aim of this study was to investigate the protein expression of chronic unpredictable mild stress (CUMS)-induced senile depression in SAMP-8 mice's frontal lobe cortex and the regulating effect of the kidney tonifying and liver dispersing (KTLD) formula.
A total of 15 male SAMP-8 mice were randomly divided into control, CUMS, and KTLD groups. CUMS and KTLD mice were subjected to CUMS for 21 days. Control group mice were kept to normal feeding. At the same time as molding, the herbal gavage (KTLD formula, 19.5 g/kg/d) was given from the beginning of the stress stimulation, while the control group and the CUMS group mice were given the same volume of saline for 21 days. Open-field testing (OFT) was used to assess the mice's depression levels. Isobaric tags for relative and absolute quantification (iTRAQ) were used to identify differentially expressed proteins (DEPs) in mice's frontal lobe cortex. Bioinformatics analysis including Gene Ontology (GO); Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) networks were utilized to study the DEPs connections.
Results revealed that mice with senile depression experienced more anxiety and depression than control mice, whereas KTLD mice had the opposite experience. Biological processes including transport, regulation of transcription, and DNA-templated were identified in both KTLD and CUMS. The KEGG enrichment study of the DEPs in KTLD revealed their involvement in the MAPK signaling pathway, glutamatergic synapse, dopaminergic synapse, axon guidance, and ribosome. KEGG pathway enrichment showed that the mechanism of senile depression and the pathway of KTLD are closely related to axonal conductance and ribosomes. According to the PPI analysis, disease-related proteins regulated by KTLD revealed that some proteins, such as GLOI1 and TRRAP, have potential interactions. This provides fresh insight into how KTLD works to cue senile depression.
KTLD treats senile depression via multiple targets and pathways, which may include regulations of 467 DEPs. Proteomics showed significant changes in protein levels in geriatric depression and after KTLD intervention. Senile depression involves the cross-linking and modulation of signal pathways, presenting a pattern of multiple pathways and multiple targets. According to a protein pathway enrichment and protein interaction model of KTLD in senile depression, KTLD is capable of treating senile depression via multiple pathways and targets.
本研究旨在探讨慢性不可预测轻度应激（CUMS）诱导 SAMP-8 小鼠额叶皮质衰老性抑郁的蛋白质表达，以及补肾疏肝方（KTLD）的调节作用。
将 15 只雄性 SAMP-8 小鼠随机分为对照组、CUMS 组和 KTLD 组。CUMS 组和 KTLD 组小鼠进行 21 天 CUMS。对照组小鼠正常饲养。同时，从应激刺激开始给予灌胃（KTLD 方，19.5 g/kg/d），对照组和 CUMS 组小鼠给予相同体积的生理盐水 21 天。旷场实验（OFT）用于评估小鼠的抑郁水平。采用同位素标记相对和绝对定量（iTRAQ）技术鉴定小鼠额叶皮质中差异表达蛋白（DEPs）。利用基因本体论（GO）、京都基因与基因组百科全书（KEGG）通路富集和蛋白质-蛋白质相互作用（PPI）网络等生物信息学分析研究 DEPs 的相互关系。
结果显示，衰老性抑郁小鼠比对照组小鼠表现出更多的焦虑和抑郁，而 KTLD 小鼠则表现出相反的情况。生物过程包括运输、转录调控和 DNA 模板。KTLD 和 CUMS 组的 DEPs 的 KEGG 富集研究表明它们参与了 MAPK 信号通路、谷氨酸能突触、多巴胺能突触、轴突导向和核糖体。KTLD 对 DEPs 的 KEGG 通路富集研究表明，衰老性抑郁的机制与 KTLD 的通路与轴突传导和核糖体密切相关。根据 PPI 分析，KTLD 调节的疾病相关蛋白表明，一些蛋白，如 GLOI1 和 TRRAP，具有潜在的相互作用。这为 KTLD 治疗衰老性抑郁的作用机制提供了新的见解。
KTLD 通过多个靶点和通路治疗衰老性抑郁，可能涉及对 467 个 DEPs 的调节。蛋白质组学显示，老年抑郁症和 KTLD 干预后蛋白质水平发生显著变化。衰老性抑郁症涉及信号通路的交联和调节，呈现出多途径、多靶点的模式。根据 KTLD 在衰老性抑郁症中的蛋白质通路富集和蛋白质相互作用模型，KTLD 能够通过多种途径和靶点治疗衰老性抑郁症。
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