目的 采用文獻數(shù)據(jù)挖掘結合網(wǎng)絡藥理學方法，預測西洋參治療糖尿病腎?。―N）的活性成分及作用機制，并建立DN斑馬魚模型進行實驗驗證。方法 檢索文獻數(shù)據(jù)結合網(wǎng)絡藥理學及分子對接技術，預測西洋參抗DN的有效成分及核心靶點；構建優(yōu)化的葡萄糖波動式誘導斑馬魚DN模型，以二甲雙胍為陽性藥，以腎水腫面積為指標評估造模是否成功，并結合腎小球濾過率、血糖、糖化血清蛋白、胰島素、肌酐、尿素氮水平及HE染色結果進行驗證；選取經(jīng)文獻數(shù)據(jù)挖掘結合網(wǎng)絡藥理學預測的關鍵活性成分擬人參皂苷F₁₁（PF₁₁）為實驗藥物，利用DN斑馬魚模型驗證其對DN的治療作用，并進一步采用實時熒光定量PCR（qRT-PCR）驗證其對主要基因的調控作用。結果 經(jīng)4%葡萄糖波動式誘導4 d建立DN斑馬魚模型，與對照組相比，模型組各考察指標均發(fā)生顯著性變化（P＜0.05、0.01），驗證模型構建成功；通過文獻數(shù)據(jù)挖掘共得到27個西洋參入血成分，經(jīng)網(wǎng)絡藥理學篩選得到64個作用靶點，利用蛋白質-蛋白質相互作用（PPI）網(wǎng)絡分析確定PF₁₁為主要活性成分，分子對接結果顯示其與核心靶點均具有較強的結合力。DN斑馬魚模型驗證結果表明，PF₁₁可顯著提高DN模型斑馬魚胰島素水平、抑制血糖升高，降低尿素氮及肌酐水平，改善腎水腫及腎小球濾過率（P＜0.05、0.01）； qRT-PCR結果進一步顯示，PF₁₁能顯著下調DN模型斑馬魚組織中信號傳導及轉錄激活蛋白3（STAT3）、表皮生長因子受體（EGFR）的mRNA表達水平（P＜0.05）。結論 建立整合網(wǎng)絡藥理學預測-斑馬魚模型驗證的抗DN活性成分篩選方法，證實西洋參中的PF₁₁具有顯著的DN治療作用。

Objective To predict the active components, therapeutic effects, and mechanisms of Panax quinquefolium in treating diabetic nephropathy (DN), by integrates literature mining and network pharmacology, and conduct experimental validation using an established zebrafish DN model. Methods Integrating bibliographic mining with network pharmacology and molecular docking, predict the active components and core targets of Panax quinquefolius(American ginseng) for combating diabetic nephropathy (DN). To establish an optimized glucose fluctuation-induced diabetic nephropathy (DN) model in zebrafish, metformin served as the positive control drug. Model establishment success was assessed based on renal edema area and further validated by evaluating glomerular filtration rate, blood glucose, glycated hemoglobin, insulin, creatinine, and blood urea nitrogen levels, in conjunction with HE staining results. Subsequently, the key active ingredient, pseudoginsenoside F₁₁ (PF₁₁), was selected as the experimental drug through literature data mining combined with network pharmacology prediction. The therapeutic effect of PF₁₁ on DN was verified using the DN zebrafish model, and its regulatory effect on major genes was further confirmed by real-time fluorescence quantitative PCR (qRT-PCR). Results Zebrafish DN model was established by subjecting fish to a 4% glucose fluctuation regimen for four days. Compared with the control group, all the examined indicators in the model group showed significant changes (P < 0.05, 0.01), which verified the successful construction of the model. Through literature data mining, a total of 27 components of Panax quinquefoliusthat enter the bloodstream were obtained. After screening by network pharmacology, 64 target sites were identified. Using protein-protein interaction (PPI) network analysis, PF₁₁ was determined to be the main active component. Molecular docking results showed that it had strong binding force with the core target sites. The results of the DN zebrafish model verification indicated that PF₁₁ could significantly increase the insulin level of DN model zebrafish, inhibit the increase of blood sugar, reduce the levels of urea nitrogen and creatinine, and improve renal edema and glomerular filtration rate (P < 0.05, 0.01). The qRT-PCR results further showed that PF₁₁ could significantly downregulate the mRNA expression levels of signal transduction and transcriptional activator protein 3 (STAT3) and epidermal growth factor receptor (EGFR) in the tissues of DN model zebrafish (P < 0.05). Conclusion Established an anti-DN active component screening method by integrating network pharmacology prediction and zebrafish model verification, and confirmed that PF₁₁ in Panax quinquefoliushas a significant therapeutic effect on DN.

R285.5

國家中醫(yī)藥管理局科技司-山東省衛(wèi)生健康委員會共建中醫(yī)藥科技項目（GZY-KJS-SD-2023-088）；山東省自然科學基金資助項目（ZR202211080026）；山東第一醫(yī)科大學學術提升計劃（2019LJ003）