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OA

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(D-gal),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 senescence-associated 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.