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基于蛋白质组学的参志灵抗抑郁作用机制研究:发现与血小板激活和脂代谢相关的蛋白。

Proteomic Analysis of the Antidepressant Effects of Shen-Zhi-Ling in Depressed Patients: Identification of Proteins Associated with Platelet Activation and Lipid Metabolism.

机构信息

Department of Clinical Pharmacology, General Hospital of Chinese People's Liberation Army, Beijing, 100853, People's Republic of China.

出版信息

Cell Mol Neurobiol. 2018 Jul;38(5):1123-1135. doi: 10.1007/s10571-018-0582-9. Epub 2018 Mar 21.

Abstract

Shen-Zhi-Ling (SZL) is a Chinese medicine formulated from a Kai-Xin-San decoction that is commonly used to treat depression caused by dual deficiencies in the heart and spleen. However, the underlying mechanisms remain unclear. We investigated biological changes in depression patients (DPs) exhibiting antidepressant responses to SZL treatment using proteomic techniques. We performed label-free quantitative proteomic analysis and liquid chromatography-tandem mass spectrometry to discover and examine altered proteins involved in depression and antidepressant treatment. Serum samples were collected from DPs, DPs who underwent 8 weeks of SZL treatment and healthy controls (HCs). The proteins that differed among the three groups were further validated by Western blot analysis. By performing multivariate analyses, we identified 12 potential serum biomarkers that were differentially expressed among the HC, DP, and SZL groups. We then confirmed the significant changes in alpha-1-antitrypsin, von Willebrand factors, apolipoprotein C-III, and alpha-2-macroglobulin among the three groups by performing Western blot analysis, which supported the proteomic results. Profiling the proteomic changes in DPs treated with SZL could improve our understanding of the pathways involved in SZL responses, such as alterations in platelet activation, inflammatory regulation, and lipid metabolism. Future studies involving larger patient cohorts are necessary to draw more definitive conclusions.

摘要

参知灵(SZL)是一种由开心散方剂制成的中药,常用于治疗心脾两虚型抑郁症。然而,其作用机制尚不清楚。我们采用蛋白质组学技术研究了对 SZL 治疗有抗抑郁反应的抑郁症患者(DPs)的生物学变化。我们进行了无标记定量蛋白质组学分析和液相色谱-串联质谱分析,以发现和检查与抑郁和抗抑郁治疗相关的改变蛋白。从 DPs、接受 8 周 SZL 治疗的 DPs 和健康对照(HCs)中采集血清样本。通过 Western blot 分析进一步验证三组之间存在差异的蛋白质。通过进行多变量分析,我们确定了 12 个潜在的血清生物标志物,它们在 HC、DP 和 SZL 组之间存在差异表达。然后,我们通过 Western blot 分析证实了 alpha-1-抗胰蛋白酶、血管性血友病因子、载脂蛋白 C-III 和 alpha-2-巨球蛋白在三组之间的显著变化,这支持了蛋白质组学结果。对接受 SZL 治疗的 DPs 的蛋白质组变化进行分析,可以加深我们对 SZL 反应相关途径的理解,例如血小板激活、炎症调节和脂质代谢的改变。未来需要更大的患者队列研究来得出更明确的结论。

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