基于 miRNA 转录组学和蛋白质组学探究金银花延缓肾衰老的作用及机制
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贵州中医药大学,贵阳 550025

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Role and mechanisms of Lonicera japonica in alleviating renal aging determined by miRNA transcriptomics and proteomics
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Guizhou University of Tranditional Chinese Medicine, Guiyang 550025, China

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    摘要:

    目的 本研究旨在探索金银花延缓肾衰老的作用及机制。 方法 采用 D-半乳糖(D-gal)腹腔注射构建小鼠肾衰老模型,同时给予金银花水煎液灌胃。 行为学实验结束后采集各组小鼠肾组织,进行酶联免疫吸附测定实验(ELISA)和 β-半乳糖苷酶染色实验( SA-β-gal)检验造模情况和金银花的作用,然后进行miRNA 转录组学和蛋白质组学测序,鉴定出具有统计学意义的差异表达 miRNA(DEMs)和差异表达蛋白质(DEPs),并利用 GO、KEGG 数据库对这些 DEMs 和 DEPs 进行功能注释和通路分析。 结果 水迷宫和负重游泳实验结果表明,与对照组相比,模型组小鼠表现出学习记忆能力下降及运动耐力降低等衰老相关特征(P<0. 05),金银花干预后,衰老相关特征显著改善(P<0. 05);ELISA 和 SA-β-gal 染色结果表明,模型组小鼠肾IL-6 含量及 SA-β-gal 染色阳性面积百分比较对照组均显著增加(P<0. 001),金银花干预后,小鼠肾 IL-6 含量及 SA-β-gal 染色阳性面积百分比均显著减少(P<0. 01)。 通过 miRNA 转录组学和蛋白质组学筛选出 11 个显著 DEMs 和 8 个显著 DEPs,对这些 DEMs 和 DEPs 的靶基因进行交集处理后,发现 miR-146b-3p / Tmprss13是 1 对关键互作分子,miR-150-3p / Brpf1、miR-1934-5p / Cln8 是两对同时受金银花下调的 miRNA 和蛋白质。GO 和 KEGG 富集分析结果显示,金银花可能通过激活 MAPK 通路中具有显著差异表达的基因 Lonicera japonica-regulated Ecsit(LjREcsit)来干扰肾衰老进程。 结论 金银花能显著延缓 D-gal 所诱导的小鼠肾衰老,其机制可能是通过抑制 miR-146b-3p 进一步激活 Tmprss13 或下调 miR-150-3p / Brpf1、miR-1934-5p / Cln8 以延缓肾衰老,LjREcsit 介导的 MAPK 信号通路的调控也是金银花延缓肾衰老的关键。

    Abstract:

    Objective To investigate the effects and underlying mechanisms of Lonicera japonica in delaying renal aging. Methods A mouse model of renal aging was established via intraperitoneal injection of D-galactose (Dgal), with concurrent administration of Lonicera japonica decoction by oral gavage. Following behavioral assessments,kidney tissues were collected from each group for enzyme-linked immunosorbent assay ( ELISA) and senescenceassociated β-galactosidase ( SA-β-gal) staining to evaluate model induction and the protective effects of Lonicera japonica. Integrated microRNA ( miRNA) transcriptomic and proteomic sequencing analyses were conducted to identify significantly differentially expressed miRNA ( DEMs) and protein ( DEPs). Functional annotation and pathway enrichment of these DEMs and DEPs were performed using gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) databases. Results Behavioral tests, including the Morris water maze and forced swimming test, revealed significant impairments in learning, memory, and exercise endurance in model mice compared with controls ( P<0. 05). Lonicera japonica markedly ameliorated these aging-related deficits ( P<0. 05). Renal interleukin (IL)-6 levels and the percentage of SA-β-gal-positive area were significantly elevated in the model group relative to the control group ( P<0. 001), and both were significantly reduced following Lonicera japonica intervention ( P<0. 01). Integrated omics analysis identified 11 significant DEMs and eight significant DEPs. Intersection analysis of target genes revealed miR-146b-3p / Tmprss13 as a key regulatory pair, while miR-150-3p / Brpf1 and miR-1934-5p / Cln8 were identified as miRNA-protein pairs concurrently downregulated by Lonicera japonica. GO and KEGG enrichment analyses indicated that Lonicera japonica may delay renal aging by activating Lonicera japonica-regulated Ecsit (LjREcsit), a differentially expressed gene involved in the mitogen-activated protein kinase (MAPK) signaling pathway. Conclusions Lonicera japonica attenuates D-gal-induced renal aging in mice,possibly via mechanisms involving inhibition of miR-146b-3p leading to activation of Tmprss13, or coordinated downregulation of miR-150-3p / Brpf1 and miR-1934-5p / Cln8. Modulation of the MAPK signaling pathway via LjREcsit also represents a critical mechanism through which Lonicera japonica exerts its renoprotective and anti-aging effects.

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刘艺萍,张冕,石小娟,吴延军,唐杰,张杰.基于 miRNA 转录组学和蛋白质组学探究金银花延缓肾衰老的作用及机制[J].中国实验动物学报,2026,34(3):398~410.

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  • 收稿日期:2025-09-05
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  • 在线发布日期: 2026-03-31
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