目的 運用生物信息學、網(wǎng)絡藥理學及實驗驗證的方法探究熟地黃Rehmanniae Radix Praeparata治療2型糖尿?。╰ype 2 diabetes mellitus，T2DM）的作用機制。方法 熟地黃的水提物ig給予T2DM小鼠，并通過超高效液相色譜-高分辨質譜（UPLC-HRMS）對入血及入胰腺成分進行辨識，在瑞士目標預測數(shù)據(jù)庫（Swiss Target Prediction）預測潛在靶點，并與基因表達綜合數(shù)據(jù)庫（Gene Expression Omnibus，GEO）中GSE15932、GSE25724數(shù)據(jù)集及比較毒物基因組學數(shù)據(jù)庫（Comparative Toxicogenomics Database，CTD）、人類基因數(shù)據(jù)庫（GeneCards）取交集獲取共同基因，并在Cytoscape中進行聚類分析，得到熟地黃入血和入胰腺靶點。對熟地黃入血和入胰腺的靶點取交集分析。在ADMETab3.0數(shù)據(jù)庫中進行毒性預測、分子對接及信使核糖核酸（messenger ribonucleic acid，mRNA）-微小核糖核酸（microRNA，miRNA）-長鏈非編碼核糖核酸（long non-coding RNA，lncRNA）互作網(wǎng)絡分析，運用基因和蛋白相互作用和功能數(shù)據(jù)庫（GeneMANIA）分析主要生物功能，并結合實時熒光定量PCR實驗驗證。結果 熟地黃可改善T2DM小鼠異常葡萄糖水平和糖耐受量。熟地黃入血化合物138個，相對應的潛在基因靶點分別為18個和1個聚類；入胰腺化合物為359個，相對應的潛在基因靶點分別為141個和6個聚類。甲狀腺素轉運蛋白基因（transthyretin，TTR）和ATP結合盒轉運蛋白B1（ATP binding cassette subfamily B member 1，ABCB1）為熟地黃入血及胰腺的交集基因靶點；得到包含6個相同miRNA及14個相同lncRNA的mRNA-miRNA-lncRNA互作網(wǎng)絡。主要生物功能涉及脂質運輸和代謝、藥物運輸、離子和神經(jīng)遞質運輸、血管過程及炎癥反應的調節(jié)等。熟地黃可影響T2DM小鼠血液和胰腺中TTR、ABCB1的mRNA表達水平。結論 TTR和ABCB1可被視為熟地黃治療T2DM的潛在作用靶點，為T2DM治療提供依據(jù)的同時為后續(xù)深入研究熟地黃作用于T2DM的相關問題提供思路。

Objective To investigate the biological mechanisms of Shudihuang (Rehmanniae Radix Praeparata) in treating type 2 diabetes mellitus (T2DM) through bioinformatics, network pharmacology, and experimental validation. Methods T2DM mice were treated with an aqueous extract of Rehmanniae Radix Praeparata by gavage, and the components that entered the blood and pancreas were identified using ultra-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). Potential targets were predicted in the Swiss Target Prediction database and compared with genes from the Gene Expression Omnibus (GEO) datasets GSE15932 and GSE25724, the Comparative Toxicogenomics Database (CTD), and the GeneCards database to identify common genes. The complex network analysis and visualization with Cytoscape software were performed intersection analysis of targets in the blood and pancreas. Toxicity prediction, molecular docking, and mRNA-miRNA-lncRNA interaction network analysis were conducted in the ADMETab3.0 database. The main biological functions were analyzed using the GeneMANIA database, supported by validation through real-time fluorescent quantitative PCR experiments.Results Rehmanniae Radix Praeparata significantly improved abnormal glucose levels and enhanced glucose tolerance in mice with T2DM. A total of 138 compounds were identified in the blood, with 18 corresponding potential gene targets and one cluster, while 359 compounds were identified in the pancreas, with 141 potential gene targets and six clusters. Transthyretin (TTR) and ATP binding cassette subfamily B member 1 (ABCB1) were identified as common gene targets in the blood and pancreas. The mRNA-miRNA-lncRNA interaction network containing six identical miRNAs and fourteen identical lncRNAs were constructed. The main biological functions involved lipid transport and metabolism, drug transport, ion and neurotransmitter transport, vascular processes, and inflammation regulation. Rehmanniae Radix Praeparata affected the mRNA expression levels of TTR and ABCB1 in the blood and pancreas of T2DM mice. Conclusion TTR and ABCB1 can be considered as potential therapeutic targets for Rehmanniae Radix Praeparata in the treatment of T2DM, providing a basis for T2DM treatment and offering insights for further research into the role of Rehmanniae Radix Praeparata in T2DM-related issues.

山西省應用基礎研究計劃項目（20210302124694）;中醫(yī)藥管理局科研課題項目（2023ZYYA2012）;山西省留學人員科技活動擇優(yōu)資助項目（重點項目）（20230034）;山西省籌資金資助歸國留學人員科研項目（2023-156）;山西省教育廳項目（2021L364）;山西中醫(yī)藥大學博士科研啟動基金項目（2023BK38）;山西中醫(yī)藥大學科技創(chuàng)新能力培育計劃（太行本草專項）（2022PY-TH-02）