基于tmt的加味丹参汤对心肌缺血再灌注损伤的定量蛋白质组学分析。

IF 2.1 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS
Xiang-Mei Zhu, Yang Tan, Yu-He Shi, Qing Li, Jue Zhu, Xiang-Dan Liu, Qiao-Zhen Tong
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引用次数: 0

摘要

背景:全世界每年约有1700万人死于冠心病,其中中国的死亡人数排名第二。心肌缺血再灌注损伤(MIRI)对心脏手术患者心功能和预后有显著影响。加味丹参汤(JWDSD)是中国临床上用于治疗MIRI多年的传统中药方剂。然而,其潜在的分子机制尚不清楚。目的:研究JWDSD给药大鼠心肌组织蛋白质组学的变化,并进行基于MIRI治疗的蛋白质组学研究。方法:结扎/释放左冠状动脉前降支,建立MIRI大鼠模型。在七天的时间里,每天给药两次。这个模型是在最后一次给药后创建的。采用生化指标和心脏组织学指标评价JWDSD改善MIRI的疗效。串联质量标记定量蛋白质组学(TMT)技术也被用于检测提取的心脏组织中的蛋白质。为了分析差异表达蛋白(DEPs),采用了生物信息学分析,包括基因本体(GO)和京都基因与基因组百科全书(KEGG)途径。此外,western blotting证实了JWDSD调控的潜在靶点。结果:JWDSD对MIRI大鼠具有一定的保护作用。共鉴定出4549个蛋白,FDR(错误发现率)≤1%。共发现20个重叠位点(模型/控制组162个,JWDSD/模型组45个)。在这些dep中,有16个受JWDSD调控。氧化石墨烯分析提供了在生物过程(BP)、细胞成分(CC)和分子功能(MF)类别中解除调节的蛋白质表达的总结。KEGG富集分析显示,中性粒细胞胞外陷阱形成、RNA聚合酶、血清素能突触和亚油酸代谢等信号通路均与MIRI大鼠JWDSD效应密切相关。此外,使用western blotting验证t细胞淋巴瘤侵袭和转移1 (TIAM1),结果与蛋白质组学数据一致。结论:本研究提示JWDSD可能通过多途径调控在MIRI治疗中发挥作用。这项工作可能为继续研究JWDSD治疗MIRI提供蛋白质组学线索。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

TMT-based quantitative proteomics analysis of the effects of Jiawei Danshen decoction myocardial ischemia-reperfusion injury.

TMT-based quantitative proteomics analysis of the effects of Jiawei Danshen decoction myocardial ischemia-reperfusion injury.

TMT-based quantitative proteomics analysis of the effects of Jiawei Danshen decoction myocardial ischemia-reperfusion injury.

TMT-based quantitative proteomics analysis of the effects of Jiawei Danshen decoction myocardial ischemia-reperfusion injury.

Background: Every year, approximately 17 million people worldwide die due to coronary heart disease, with China ranking second in terms of the death toll. Myocardial ischemia-reperfusion injury (MIRI) significantly influences cardiac function and prognosis in cardiac surgery patients. Jiawei Danshen Decoction (JWDSD) is a traditional Chinese herbal prescription that has been used clinically for many years in China to treat MIRI. The underlying molecular mechanisms, however, remain unknown. To investigate the proteomic changes in myocardial tissue of rats given JWDSD for MIRI therapy-based proteomics.

Methods: MIRI rat model was created by ligating/releasing the left anterior descending coronary artery. For seven days, the drugs were administered twice daily. The model was created following the last drug administration. JWDSD's efficacy in improving MIRI was evaluated using biochemical markers and cardiac histology. Tandem mass tag-based quantitative proteomics (TMT) technology was also used to detect proteins in the extracted heart tissue. To analyze differentially expressed proteins (DEPs), bioinformatics analysis, including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways, were employed. Furthermore, western blotting confirmed the potential targets regulated by JWDSD.

Results: The histopathologic characteristics and biochemical data showed JWDSD's protective effects on MIRI rats. A total of 4549 proteins were identified with FDR (false discovery rate) ≤1%. Twenty overlapping were identified (162 DEPs and 45 DEPs in Model/Control or JWDSD/Model group, respectively). Of these DEPs, 16 were regulated by JWDSD. GO analysis provided a summary of the deregulated protein expression in the categories of biological process (BP), cell component (CC), and molecular function (MF). KEGG enrichment analysis revealed that the signaling pathways of neutrophil extracellular trap formation, RNA polymerase, serotonergic synapse, and linoleic acid metabolism are all closely related to JWDSD effects in MIRI rats. Furthermore, T-cell lymphoma invasion and metastasis 1 (TIAM1) was validated using western blotting, and the results were consistent with proteomics data.

Conclusions: Our study suggests that JWDSD may exert therapeutic effects through multi-pathways regulation in MIRI treatment. This work may provide proteomics clues for continuing research on JWDSD in treating MIRI.

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来源期刊
Proteome Science
Proteome Science 生物-生化研究方法
CiteScore
2.90
自引率
0.00%
发文量
17
审稿时长
4.5 months
期刊介绍: Proteome Science is an open access journal publishing research in the area of systems studies. Proteome Science considers manuscripts based on all aspects of functional and structural proteomics, genomics, metabolomics, systems analysis and metabiome analysis. It encourages the submissions of studies that use large-scale or systems analysis of biomolecules in a cellular, organismal and/or environmental context. Studies that describe novel biological or clinical insights as well as methods-focused studies that describe novel methods for the large-scale study of any and all biomolecules in cells and tissues, such as mass spectrometry, protein and nucleic acid microarrays, genomics, next-generation sequencing and computational algorithms and methods are all within the scope of Proteome Science, as are electron topography, structural methods, proteogenomics, chemical proteomics, stem cell proteomics, organelle proteomics, plant and microbial proteomics. In spite of its name, Proteome Science considers all aspects of large-scale and systems studies because ultimately any mechanism that results in genomic and metabolomic changes will affect or be affected by the proteome. To reflect this intrinsic relationship of biological systems, Proteome Science will consider all such articles.
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