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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英文版,2026,46(1):31-41.[Click to copy
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| 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 |
| 董佳凝,卫燕东,赵怡蕊,侯岚炜,张鑫 |
| (山西中医药大学第三临床学院, 山西 晋中 030619;山西省中西医结合医院肾病科一病区, 山西 太原 030000) |
| 摘要: |
| 目的 探讨黄芪-桃仁-苦参（HTK）角药配伍抗肾纤维化（RF）的作用机制。方法 利用TCMSP和Swiss Target Prediction数据库筛选药物的活性成分及作用靶点；使用GeneCard、OMIM、TTD数据库检索RF的相关靶点；对收集的药物靶点和疾病靶点取其交集获得潜在作用靶点；通过STRING数据库构建靶点蛋白质-蛋白质相互作用（PPI）网络、DAVID分析平台进行GO和KEGG信号通路富集分析。将32只SD大鼠随机分为空白对照组、模型组、达格列净组和HTK组，除空白对照组外，其他3组先采用腺嘌呤连续灌胃28 d诱导RF大鼠模型，造模成功后，达格列净组和HTK组持续药物灌胃治疗8周，模型组和空白对照组给予等体积生理盐水灌胃。检测大鼠血尿素氮（BUN）、血肌酐（Scr）水平；HE染色、Masson染色、免疫组化观察大鼠肾脏病理变化；Western blot检测肾组织中磷脂酰肌醇3-激酶／蛋白激酶B（PI3K/Akt）信号通路对RF的调控作用。结果 网络药理学结果显示，HTK治疗RF有256个潜在作用靶点，肿瘤蛋白p53（TP53）、热激蛋白90α（HSP90α）、Akt1等核心靶点较为关键；KEGG预测HTK可能通过癌症通路、EGFR酪氨酸激酶抑制剂耐药性、PI3K/Akt信号通路等发挥抗RF作用。动物实验结果显示，与空白对照组相比，模型组大鼠肾组织出现明显胶原纤维沉积，BUN、Scr水平增高（P＜0.01），Ⅰ型胶原蛋白（COL-Ⅰ）、α-平滑肌肌动蛋白（α-SMA）表达升高（P＜0.01），PI3K、p-PI3K、Akt、p-Akt蛋白表达升高（P＜0.01）；与模型组相比，达格列净组、HTK组肾组织胶原纤维沉积有所改善，BUN、Scr水平下降（P＜0.01），COL-Ⅰ、α-SMA表达降低（P＜0.01），PI3K、p-PI3K、Akt、p-Akt蛋白表达降低（P＜0.05，P＜0.01）。结论 HTK配伍可以改善肾纤维化，其作用机制可能与调节PI3K/Akt信号通路相关蛋白的表达促进胶原纤维降解有关。 |
| 关键词: 肾纤维化 黄芪 桃仁 苦参 PI3K/Akt信号通路 网络药理学 |
| DOI：10.3969/j.issn.1674-070X.2026.01.005 |
| Received:October 08, 2025 |
| 基金项目:山西省卫生健康委员会中医药科研项目（2025ZYYB032）；山西省中医药管理局科研项目（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）。 |
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| 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 |
| DONG Jianing, WEI Yandong, ZHAO Yirui, HOU Lanwei, ZHANG Xin |
| (The Third Clinical College of Shanxi University of Chinese Medicine, Jinzhong, Shanxi 030619, China;The First Ward of Department of Nephrology, Shanxi Provincial Integrated Traditional Chinese Medicine and Western Medicine Hospital, Taiyuan, Shanxi 030000, China) |
| 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. |
| Key words: renal fibrosis Huangqi (Astragali Radix) Taoren (Persicae Semen) Kushen (Sophorae Flavescentis Radix) PI3K/Akt signaling pathway network pharmacology |
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