目的基于微小RNA(microRNA,miRNA)高通量测序技术,探讨黄芪-丹参药对通过调控miRNA改善高血压肾损害的作用机制。方法以9只WKY大鼠作为对照组,将自发性高血压大鼠随机分为模型组和黄芪-丹参药对(3.4 g/kg)组,每组9只;黄芪-丹参药对组给...目的基于微小RNA(microRNA,miRNA)高通量测序技术,探讨黄芪-丹参药对通过调控miRNA改善高血压肾损害的作用机制。方法以9只WKY大鼠作为对照组,将自发性高血压大鼠随机分为模型组和黄芪-丹参药对(3.4 g/kg)组,每组9只;黄芪-丹参药对组给予黄芪-丹参药对进行干预,观察各组大鼠血压及肾组织病理变化,并对各组大鼠肾组织进行miRNA测序。结果经黄芪-丹参药对干预4周后,与模型组比较,大鼠血压显著降低(P<0.01),大鼠肾小球分叶不明显,系膜区增生减轻。与对照组相比,模型组共筛选出115个差异表达miRNA,其中68个差异表达miRNA上调、47个差异表达miRNA下调;与模型组相比,黄芪-丹参药对组筛选得到91个差异表达miRNA,其中67个差异表达miRNA上调、24个差异表达miRNA下调。差异表达miRNA的qRT-PCR验证结果显示,各组大鼠肾组织miRNA-142-5p、miRNA-3585-5p、miRNA-219a-5p、miRNA-122-5p和miRNA-125b-1-3p表达与miRNA测序结果趋势一致。差异表达miRNA的靶基因预测及功能富集结果显示,基因本体(gene ontology,GO)功能主要富集于阴离子跨膜转运、突触前、蛋白质丝氨酸/苏氨酸激酶活性等方面;京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路主要富集于哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)、自噬、单磷酸腺苷活化蛋白激酶(adenosine monophosphate-activated protein kinase,AMPK)信号通路等途径。结论miR-219a-5p、miR-3585-5p和miR-142-5p可能是黄芪-丹参药对延缓高血压肾损害进程的直接靶点。展开更多
To elucidate the mechanism underlying the therapeutic impact of Astragalus-Danshen in chronic glomerulonephritis(CGN),a comprehensive exploration was conducted utilizing network pharmacology.The TCMSP database was emp...To elucidate the mechanism underlying the therapeutic impact of Astragalus-Danshen in chronic glomerulonephritis(CGN),a comprehensive exploration was conducted utilizing network pharmacology.The TCMSP database was employed to aggregate the chemical constituents and targets associated with Astragalus and Danshen.Simultaneously,disease targets specific to CGN were sourced from the Genecards database.The convergence of these datasets yielded a set of intersection genes,representing potential targets for CGN treatment through Astragalus-Danshen formulations.Subsequently,protein interaction networks and“chemical composition-target”networks were meticulously constructed.Core targets were subjected to GO and KEGG enrichment analyses.The investigation revealed a total of 240 targets corresponding to 20 and 65 chemical components of Astragalus and Danshen,respectively.From this pool,86 potential targets associated with CGN treatment were discerned,ultimately identifying 29 core targets.Noteworthy among these were TNF,JUN,TP53,IL1B,RELA,MMP9,CASP3,IL10,MAPK14,MYC,and TGFB1.KEGG enrichment analysis illuminated pathways pertinent to CGN,encompassing the IL-17 signaling pathway,TNF signaling pathway,and the AGE-RAGE signaling pathway in diabetic complications.In summary,Astragalus-Danshen exhibited a potential anti-inflammatory and renoprotective effect on CGN,particularly through modulating the IL-17 signaling pathway,TNF signaling pathway,and AGE-RAGE signaling pathway in diabetic complications,involving key regulators such as TNF,JUN,TP53,IL1B,MAPK14,and others.展开更多
文摘目的基于微小RNA(microRNA,miRNA)高通量测序技术,探讨黄芪-丹参药对通过调控miRNA改善高血压肾损害的作用机制。方法以9只WKY大鼠作为对照组,将自发性高血压大鼠随机分为模型组和黄芪-丹参药对(3.4 g/kg)组,每组9只;黄芪-丹参药对组给予黄芪-丹参药对进行干预,观察各组大鼠血压及肾组织病理变化,并对各组大鼠肾组织进行miRNA测序。结果经黄芪-丹参药对干预4周后,与模型组比较,大鼠血压显著降低(P<0.01),大鼠肾小球分叶不明显,系膜区增生减轻。与对照组相比,模型组共筛选出115个差异表达miRNA,其中68个差异表达miRNA上调、47个差异表达miRNA下调;与模型组相比,黄芪-丹参药对组筛选得到91个差异表达miRNA,其中67个差异表达miRNA上调、24个差异表达miRNA下调。差异表达miRNA的qRT-PCR验证结果显示,各组大鼠肾组织miRNA-142-5p、miRNA-3585-5p、miRNA-219a-5p、miRNA-122-5p和miRNA-125b-1-3p表达与miRNA测序结果趋势一致。差异表达miRNA的靶基因预测及功能富集结果显示,基因本体(gene ontology,GO)功能主要富集于阴离子跨膜转运、突触前、蛋白质丝氨酸/苏氨酸激酶活性等方面;京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路主要富集于哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)、自噬、单磷酸腺苷活化蛋白激酶(adenosine monophosphate-activated protein kinase,AMPK)信号通路等途径。结论miR-219a-5p、miR-3585-5p和miR-142-5p可能是黄芪-丹参药对延缓高血压肾损害进程的直接靶点。
基金Specialized Research on Traditional Chinese Medicine in Henan Province(Grant No.KJGG108).
文摘To elucidate the mechanism underlying the therapeutic impact of Astragalus-Danshen in chronic glomerulonephritis(CGN),a comprehensive exploration was conducted utilizing network pharmacology.The TCMSP database was employed to aggregate the chemical constituents and targets associated with Astragalus and Danshen.Simultaneously,disease targets specific to CGN were sourced from the Genecards database.The convergence of these datasets yielded a set of intersection genes,representing potential targets for CGN treatment through Astragalus-Danshen formulations.Subsequently,protein interaction networks and“chemical composition-target”networks were meticulously constructed.Core targets were subjected to GO and KEGG enrichment analyses.The investigation revealed a total of 240 targets corresponding to 20 and 65 chemical components of Astragalus and Danshen,respectively.From this pool,86 potential targets associated with CGN treatment were discerned,ultimately identifying 29 core targets.Noteworthy among these were TNF,JUN,TP53,IL1B,RELA,MMP9,CASP3,IL10,MAPK14,MYC,and TGFB1.KEGG enrichment analysis illuminated pathways pertinent to CGN,encompassing the IL-17 signaling pathway,TNF signaling pathway,and the AGE-RAGE signaling pathway in diabetic complications.In summary,Astragalus-Danshen exhibited a potential anti-inflammatory and renoprotective effect on CGN,particularly through modulating the IL-17 signaling pathway,TNF signaling pathway,and AGE-RAGE signaling pathway in diabetic complications,involving key regulators such as TNF,JUN,TP53,IL1B,MAPK14,and others.
