肾性高血压大鼠粪便中miRNA的差异表达及富集分析  

Differential Expression and Cluster Analysis of miRNA in Fecal Stool of Rats with Renal Hypertension

作　　者：陈张军 王占黎 胡海[1] 于慧[1] Chen Zhangjun;Wang Zhanli;Hu Hai;Yu Hui(School of Basic Medicine and Forensic Medicine,Baotou Medical College,Baotou 014040;Key Laboratory of Disease Related Biomarkers of Inner Mongolia Autonomous Region,Baotou 014040)

机构地区：[1]包头医学院基础医学院与法医学院,包头014040 [2]内蒙古自治区疾病相关生物标志物重点实验室,包头014040

出　　处：《国际老年医学杂志》2023年第5期518-523,共6页International Journal of Geriatrics

基　　金：国家自然科学基金资助项目(82060084,82260092)。

摘　　要：目的本研究旨在检测肾性高血压大鼠粪便中异常表达的miRNA,并对其靶基因进行生物学功能及通路富集分析。方法将16只SD大鼠随机分为假手术组(Sham组,8只)、模型组(Model组,8只),Sham组分离左肾动脉不结扎,Model组分离左肾动脉并用0.2 mm银夹结扎。收集粪便,并用miRNA测序筛选差异表达miRNA,对显著差异表达的miRNA进行靶基因预测,对靶基因进行GO功能和KEGG通路富集。结果术后血压比较,Model组收缩压水平高于Sham组,差异有统计学意义(P<0.05)。粪便miRNA差异分析中,Model组有6个差异表达的miRNA(P<0.001),其中4个上调miRNA(rno-miR-335-5p、rno-miR-466-3p、rno-miR-218a-5p、rno-miR-3557-3p)、2个下调miRNA(rno-let-7a-5p、rno-miR-200b-5p),共预测miRNA下游靶基因288个,GO富集主要集中在蛋白质定位、NK T细胞分化和酶活性等方面;KEGG通路富集主要集中在mTOR信号通路、MAPK信号通路等。结论在肾性高血压大鼠粪便中miRNA呈显著差异表达,其靶基因可能通过免疫细胞活化的生物学功能及mTOR和MAPK等信号通路参与高血压的发展。Objective To detect aberrantly expressed miRNAs in feces of renally hypertensive rats and perform biological function and pathway enrichment analysis of their target genes,this study was carried out.Methods 16 SD rats were randomly divided into sham operation group(Sham group,8)and model group(Model group,8).The left renal artery was separated without ligation in sham operation group,and the left renal artery was separated and ligated with 0.2 mm silver clip in model group.Feces were collected and differentially expressed miRNAs were screened by miRNA sequencing.Target genes of significantly differentially expressed miRNAs were predicted,and GO function and KEGG pathway enrichment of target genes were performed.Results Compared with the postoperative blood pressure,the systolic blood pressure level in the Model group was higher than that in the Sham group,and the difference was statistically significant(P<0.05).In the differential analysis of fecal miRNAs,there were 6 differentially expressed miRNAs in the Model group(P<0.001),including 4 up-regulated miRNAs(rno-miR-335-5p,rno-miR-466-3p,rno-miR-218a-5p,rno-miR-3557-3p)and 2 down-regulated miRNAs(rno-let-7a-5p,rno-miR-200b-5p).A total of 288 downstream target genes of miRNAs were predicted.GO enrichment mainly focused on protein localization,NK T cell differentiation and enzyme activity.The enrichment of KEGG pathway was mainly concentrated in mTOR signaling pathway,MAPK signaling pathway and so on.Conclusion miRNA is significantly differentially expressed in the feces of renal hypertensive rats,and its target genes may be involved in the development of hypertension through the biological function of immune cell activation and signaling pathways such as mTOR and MAPK.

关 键 词：肾性高血压 MIRNA 靶基因 

分 类 号：R544.14[医药卫生—心血管疾病]