目的:分析小鼠肾脏衰老过程中长链非编码RNA（lncRNA）的差异表达情况，探索肾脏衰老的机制。方法:随机选取3、12和24月龄C57BL/6雄性小鼠各5只（体重均为25 g左右），采用PAS、Masson、半乳糖苷酶（SA-β-gal）染色方法检测小鼠肾脏病理及细胞衰老情况。高通量测序得到3组小鼠组间差异表达的lncRNA及其表达丰度值，绘制热图。采用实时荧光定量PCR（qRT-PCR）验证差异表达的lncRNA。构建竞争性内源性RNA（competitive endogenous RNA，ceRNA）网络（包含lncRNA、miRNA和mRNA），GO、KEGG富集分析预测差异表达lncRNA靶基因的生物学功能。结果:肾脏病理染色结果显示，随着小鼠月龄增加，肾小球系膜基质增多，基底膜增厚，肾小球硬化逐渐加重；肾脏纤维化逐渐加重；SA-β-gal染色阳性区域逐渐增加。测序结果显示，3组小鼠间差异表达的lncRNA共938个已知的lncRNA和542个未知的lncRNA。其中，与3月龄小鼠相比，12月龄小鼠有33个lncRNA表达上调，43个lncRNA表达下调；与3月龄小鼠相比，24月龄小鼠有130个lncRNA表达上调，91个lncRNA表达下调；与12月龄小鼠相比，24月龄小鼠有36个lncRNA表达上调，22个lncRNA表达下调。qRT-PCR验证的差异表达倍数较大、表达量较高的10个lncRNA与测序结果一致。GO富集分析结果显示，3组差异表达的lncRNA靶基因多定位于细胞核和细胞质，也可能通过与蛋白结合来发挥作用，还可能参与各种蛋白磷酸化、细胞周期、转录、转录调节等过程。KEGG富集分析结果显示，3组差异表达lncRNA的靶基因富集明显的通路是与肾脏衰老密切相关的Rap1信号通路、FOXO信号通路和MAPK信号通路。结论:不同月龄小鼠肾脏lncRNA表达存在显著差异，lncRNA的差异表达可能参与肾脏衰老的发生。“,”Objective:To analyze the differentally expressed long non-coding RNA (lncRNA) among mice of different ages and explore the mechanism of kidney aging.Methods:Male C57BL/6 mice aged 3-month-old (n n=5), 12-month-old (n n=5) and 24-month-old (n n=5) (each weighting about 25 g) were randomly selected. PAS staining, Masson staining and senescence associated β-galactosidase (SA-β-gal) staining were used to detect the pathology and cell senescence of mice kidney. High throughput sequencing was performed to detect the differentially expressed lncRNA and their fragments per kilobase million. Real-time quantitative PCR was used to verify the differentially expressed lncRNA. Competitive endogenous RNA (ceRNA) network, which consisted of lncRNA, miRNA and mRNA was built. GO and KEGG enrichment analysis method were used to predict the biological function of differentially expressed lncRNA.n Results:PAS staining and Masson staining showed the development of kidney fibrosis, and SA-β-gal staining positive region was increased significantly as age increased. There were 938 known lncRNA and 542 novel lncRNA differentially expressed among different ages' mouse kidney. Compared with 3-month-old mice, 33 lncRNA were up-regulated and 43 lncRNA were down-regulated in 12-month-old mice. Compared with 3-month-old mice, 130 lncRNA were up-regulated and 91 lncRNA were down-regulated in 24-month-old mice. Compared with 12-month-old mice, 36 lncRNA were up-regulated and 22 lncRNA were down-regulated in 24-month-old mice. The results of qRT-PCR about verified 10 lncRNAs with larger differential expression multiples and higer expression levels were consistent with the sequencing data. GO enrichment analysis showed that the target genes of lncRNA differentially expressed in the three groups were mostly located in the nucleus and cytoplasm, and might play a role by binding to proteins or participate in various protein phosphorylation, cell cycle, transcription, transcription regulation and other processes. KEGG enrichment analysis showed that the target genes of lncRNA differentially expressed in the three group were significantly enriched in Rap1 signaling pathway, FOXO signaling pathway and MAPK signaling pathway, which were closely related to kidney aging.Conclusion:There are significant differences in expression of lncRNA among the kidney of different ages mice, which are involved in the occurrence of renal senescence.