罗沙司他联合当归补血汤对AR和NR3C2基因表达的影响

Effects of rosastatin combined with Danggui Buxue Tang on expressions of AR and NR3C2

目的基于网络药理学预测罗沙司他联合当归补血汤治疗肾性贫血的作用机制,并进行动物实验验证。方法运用PharmMapper、TCMSP、STRING、GeneCards、OMIM及DAVID数据库进行靶点蛋白及信号通路分析,探讨罗沙司他联合当归补血汤治疗肾性贫血的潜在作用靶点,构建“药物-靶点-疾病”模型,预测可能的生物途径。进行大鼠实验验证关键靶点和作用机制。结果网络药理学研究发现,罗沙司他联合当归补血汤主要通过NR3C2、AR、NR1I3和RUNX1T1共4个共同的蛋白靶点,PI3K-Akt等16条共同信号通路发挥治疗肾性贫血的作用。罗沙司他联合当归补血汤通过上调靶蛋白AR表达、抑制靶蛋白NR3C2的表达来发挥作用。结论罗沙司他联合当归补血汤可通过抑制NR3C2的表达、上调AR的表达来改善机体的炎症及氧化应激,进而发挥治疗肾性贫血的作用。

Objective To predict the mechanism of roxadustat combined with Danggui Buxue Tang against renal anemia(RA)based on network pharmacology,and to verify the result via animal experiments.Methods The target proteins and signaling pathways were retrieved from PharmMapper,TCMSP,STRING,GeneCards,OMIM and DAVID database.The potential targets of roxadustat combined with Danggui Buxue Tang in treating RA were explored.A“drug-target-pathway”model was established to predict possible biological pathways.Subsequently,rat experiments were conducted to validate the main targets.Results Network pharmacology research found that the combination of roxadustat and Danggui Buxue Tang mainly exerted therapeutic effects on renal anemia through four common protein targets,namely NR3C2,AR,NR1I3,and RUNX1T1,as well as through 16 common signaling pathways such as PI3K-Akt pathway.The combination of roxadustat and Danggui Buxue Tang could upregulate the expression of target protein AR but inhibit the expression of target protein NR3C2 to exert its effects.Conclusion The combination of roxadustat and Danggui Buxue Tang can improve inflammation and oxidative stress in the body by inhibiting the expression of NR3C2 and upregulating the expression of AR,thereby exerting a therapeutic effect on renal anemia.