中药药理与临床2025，Vol.41Issue(11)：21-26,6.
武威汉简瘀方靶向Sirt1抑制PI3K/AKT信号通路对高血压肾损伤的影响
Effect of Wuwei Hanjian Yu Fang Targeting Sirt1 to Inhibit PI3K/AKT Signaling Pathway on Hypertensive Renal Injury
摘要
Abstract
Objective:To predict and screen the potential molecular targets of Wuwei Hanjian Yu Fang(武威汉简瘀方)for intervening in hyper-tensive renal injury through network pharmacology and molecular docking technology and analyze the effects of the formula on the expression of potential targets and pathways in hypertensive renal injury through animal experiments.Methods:The TCMSP and PubChem databases were used to obtain active ingredients of Wuwei Hanjian Yu Fang,and target conversion was carried out.The Gene Cards and OMIM databases were used to obtain the targets of hypertensive renal injury.The intersection targets of Wuwei Hanjian Yu Fang and hypertensive renal injury were employed to construct an intersection target interaction network and topology analysis and get key targets.The Auto Dock software was used for the molecular docking of key compounds and key protein receptors of hypertensive renal injury,and the GO function and KEGG path-way enrichment were analyzed on key targets.The results of network pharmacology and molecular docking above were verified via the animal experiment.Wuwei Hanjian Yu Fang granules were orally administrated on spontaneously hypertensive rats(SHR)for eight weeks,and then the levels of blood pressure,urinary protein,creatinine,and urea nitrogen were detected.The morphological changes of renal tissue in SHR rats were observed by transmission electron microscopy,and the expression levels of the screened key targets and related signaling pathways were detected by Western Blot and RT-PCR.Results:Quercetin,kaempferol,β-sitosterol,and other main active ingredients of Wuwei Hanjian Yu Fang were docked well with Mdm2,Akt1,Sirt1,and other key targets.Specifically,quercetin showed the most stable binding with these tar-gets.The key targets were mainly involved in the regulation of autophagy,negative regulation of macrophage,and other biological processes and were enriched in the signaling pathways such as CellμLar senescence,PI3K-AKT,AMPK,and P53.Animal experimental results showed that compared with the normal control group,the model control group displayed significantly elevated blood pressure level(P<0.01),signifi-cantly increased contents of urinary protein,creatinine,and urea nitrogen(P<0.01),exacerbated endothelial damage in the glomerular and tubular vasculature,up-regulated Mdm2 and Akt1 mRNA expressions in renal tissue,down-regulated Sirt1 mRNA expression(P<0.01),in-creased P-PI3K,P-AKT1,and MDM2 protein expressions,and decreased SIRT1 protein expression(P<0.01).Compared with the model control group,the rats after the intervention of the formula displayed significantly decreased blood pressure levels(P<0.01 or P<0.05),re-duced contents of urinary protein,creatinine,and urea nitrogen(P<0.01 or P<0.05),down-regulated Mdm2 and Akt1 mRNA expressions in renal tissue,up-regulated Sirt1 mRNA expression(P<0.01 or P<0.05),decreased P-PI3K,P-AKT1,and MDM2 protein expressions,and in-creased SIRT1 protein expression(P<0.01 or P<0.05).Conclusion:Wuwei Hanjian Yu Fang has a certain protective effect on hypertensive renal injury,which may be exerted through up-regulation of Sirt1 expression by quercetin as the core active ingredient to inhibit the PI3K-AKT-MDM2 signaling pathway.关键词
武威汉简瘀方/高血压肾损伤/网络药理学/蛋白激酶/磷脂酰肌醇3-激酶/鼠双微体基因2蛋白/沉默调节蛋白1Key words
Wuwei Hanjian Yu Fang(武威汉简瘀方)/Hypertensive renal injury/Network pharmacology/Protein kinase/Phosphatidylinositol 3-kinase/Murine double minute 2/Silent information regulator 1引用本文复制引用
沈路凡,徐静,马睿玲,侯明双,吕红英,贾冠军,寇雨顺,康万荣,伊琳..武威汉简瘀方靶向Sirt1抑制PI3K/AKT信号通路对高血压肾损伤的影响[J].中药药理与临床,2025,41(11):21-26,6.基金项目
国家自然科学基金资助项目(编号:82160842) （编号:82160842）
甘肃省中医药科研项目(编号:GZKP-2022-40) （编号:GZKP-2022-40）
甘肃省联合科研基金一般项目(编号:23JRRA1521). （编号:23JRRA1521）
