目的 采用文獻(xiàn)數(shù)據(jù)挖掘結(jié)合網(wǎng)絡(luò)藥理學(xué)方法，預(yù)測(cè)西洋參治療糖尿病腎?。―N）的活性成分及作用機(jī)制，并建立DN斑馬魚模型進(jìn)行實(shí)驗(yàn)驗(yàn)證。方法 檢索文獻(xiàn)數(shù)據(jù)結(jié)合網(wǎng)絡(luò)藥理學(xué)及分子對(duì)接技術(shù)，預(yù)測(cè)西洋參抗DN的有效成分及核心靶點(diǎn)；構(gòu)建優(yōu)化的葡萄糖波動(dòng)式誘導(dǎo)斑馬魚DN模型，以二甲雙胍為陽(yáng)性藥，以腎水腫面積為指標(biāo)評(píng)估造模是否成功，并結(jié)合腎小球?yàn)V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(jié)果進(jìn)行驗(yàn)證；選取經(jīng)文獻(xiàn)數(shù)據(jù)挖掘結(jié)合網(wǎng)絡(luò)藥理學(xué)預(yù)測(cè)的關(guān)鍵活性成分?jǐn)M人參皂苷F₁₁（PF₁₁）為實(shí)驗(yàn)藥物，利用DN斑馬魚模型驗(yàn)證其對(duì)DN的治療作用，并進(jìn)一步采用實(shí)時(shí)熒光定量PCR（qRT-PCR）驗(yàn)證其對(duì)主要基因的調(diào)控作用。結(jié)果 經(jīng)4%葡萄糖波動(dòng)式誘導(dǎo)4 d建立DN斑馬魚模型，與對(duì)照組相比，模型組各考察指標(biāo)均發(fā)生顯著性變化（P＜0.05、0.01），驗(yàn)證模型構(gòu)建成功；通過文獻(xiàn)數(shù)據(jù)挖掘共得到27個(gè)西洋參入血成分，經(jīng)網(wǎng)絡(luò)藥理學(xué)篩選得到64個(gè)作用靶點(diǎn)，利用蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)分析確定PF₁₁為主要活性成分，分子對(duì)接結(jié)果顯示其與核心靶點(diǎn)均具有較強(qiáng)的結(jié)合力。DN斑馬魚模型驗(yàn)證結(jié)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?yàn)V過率（P＜0.05、0.01）； qRT-PCR結(jié)果進(jìn)一步顯示，PF₁₁能顯著下調(diào)DN模型斑馬魚組織中信號(hào)傳導(dǎo)及轉(zhuǎn)錄激活蛋白3（STAT3）、表皮生長(zhǎng)因子受體（EGFR）的mRNA表達(dá)水平（P＜0.05）。結(jié)論 建立整合網(wǎng)絡(luò)藥理學(xué)預(yù)測(cè)-斑馬魚模型驗(yàn)證的抗DN活性成分篩選方法，證實(shí)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(guó)家中醫(yī)藥管理局科技司-山東省衛(wèi)生健康委員會(huì)共建中醫(yī)藥科技項(xiàng)目（GZY-KJS-SD-2023-088）；山東省自然科學(xué)基金資助項(xiàng)目（ZR202211080026）；山東第一醫(yī)科大學(xué)學(xué)術(shù)提升計(jì)劃（2019LJ003）