湖南中医药大学学报2026，Vol.46Issue(1)：31-41,11.DOI:10.3969/j.issn.1674-070X.2026.01.005
基于PI3K/Akt信号通路探讨"黄芪-桃仁-苦参"角药配伍抗肾纤维化的作用机制
Mechanism of action of the Huangqi(Astragali Radix)-Taoren(Persicae Semen)-Kushen(Sophorae Flavescentis Radix)tri-herb combination against renal fibrosis based on the PI3K/Akt signaling pathway
摘要
Abstract
Objective To explore the mechanism of action of the Huangqi(Astragali Radix)-Taoren(Persicae Semen)-Kushen(Sophorae Flavescentis Radix)(HTK)tri-herb combination against renal fibrosis(RF).Methods Active ingredients and targets of drugs were screened using the TCMSP and SwissTargetPrediction databases;RF-related targets were retrieved from the GeneCards,OMIM,and TTD databases;the intersection of drug targets and disease targets was identified to obtain potential therapeutic targets;a protein-protein interaction(PPI)network was constructed using the STRING database,and the GO and KEGG pathway enrichment analyses were performed using the DAVID analysis platform.Thirty-two SD rats were randomly divided into blank control,model,dapagliflozin,and HTK groups.Except for the blank control group,the other three groups were first induced with an RF rat model via continuous gavage administration of adenine for 28 days.After successful modeling,the dapagliflozin and HTK groups received continuous drug gavage treatment for 8 weeks,while the blank control and model groups were administered an equal volume of normal saline via gavage.Blood urea nitrogen(BUN)and serum creatinine(Scr)levels were measured.Renal pathological changes were observed using HE staining,Masson's trichrome staining,and immunohistochemistry(IHC).Western blot analysis was performed to detect the regulatory role of the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway in RF.Results Network pharmacology results indicated 256 potential targets for HTK in treating RF.Core targets such as tumor protein p53(TP53),heat shock protein 90 alpha(HSP90AA1),and protein kinase B1(Akt1)were identified as crucial.KEGG prediction indicated that HTK exerted anti-RF effects through pathways including pathways in cancer,EGFR tyrosine kinase inhibitor resistance,and the PI3K/Akt signaling pathway.Animal experiments revealed that compared with the blank control group,rats in the model group exhibited significant collagen fiber deposition in renal tissue,elevated BUN and Scr levels(P<0.01),increased expression of collagen type I(COL-I)and α-smooth muscle actin(α-SMA)(P<0.01),and up-regulated protein expression of PI3K,p-PI3K,Akt,and P-Akt(P<0.01).Compared with the model group,the dapagliflozin and HTK groups showed ameliorated renal collagen fiber deposition,decreased BUN and Scr levels(P<0.01),reduced COL-I and α-SMA expression(P<0.01),and down-regulated protein expression of PI3K,p-PI3K,Akt,and P-Akt(P<0.05,P<0.01).Conclusion HTK combination therapy can ameliorate renal fibrosis,and its mechanism of action may be related to promoting collagen fiber degradation through regulating the expression of proteins associated with the PI3K/Akt signaling pathway.关键词
肾纤维化/黄芪/桃仁/苦参/PI3K/Akt信号通路/网络药理学Key words
renal fibrosis/Huangqi(Astragali Radix)/Taoren(Persicae Semen)/Kushen(Sophorae Flavescentis Radix)/PI3K/Akt signaling pathway/network pharmacology分类
医药卫生引用本文复制引用
董佳凝,卫燕东,赵怡蕊,侯岚炜,张鑫..基于PI3K/Akt信号通路探讨"黄芪-桃仁-苦参"角药配伍抗肾纤维化的作用机制[J].湖南中医药大学学报,2026,46(1):31-41,11.基金项目
山西省卫生健康委员会中医药科研项目(2025ZYYB032) （2025ZYYB032）
山西省中医药管理局科研项目(2024ZYYC028) （2024ZYYC028）
山西中医药大学科技创新能力培育计划"国家自然科学基金培育专项"(2024PY-NS-008). （2024PY-NS-008）
