目的 基于網(wǎng)絡藥理學、分子對接及細胞實驗探究當歸補血湯抗糖尿病腎?。―N）的作用機制。方法 利用中藥系統(tǒng)藥理學數(shù)據(jù)庫與分析平臺（TCMSP）及中藥綜合數(shù)據(jù)庫（TCMID），篩選當歸補血湯中黃芪與當歸的有效成分；通過UniProt和Swiss Target Prediction數(shù)據(jù)庫，識別活性成分的相關(guān)靶點；利用GeneCards與OMIM數(shù)據(jù)庫預測DN的潛在靶點；基于獲取的數(shù)據(jù)，利用STRING數(shù)據(jù)庫以及Cytoscape軟件構(gòu)建蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡及“藥物-活性成分-靶點”網(wǎng)絡。利用DAVID數(shù)據(jù)庫對上述靶點進行了基因本體（GO）注釋及京都基因與基因組百科全書（KEGG）通路富集分析。通過分子對接實驗及細胞實驗進行驗證，揭示當歸補血湯治療DN的作用機制。結(jié)果 網(wǎng)絡藥理學分析，得到當歸補血湯32個活性成分，與疾病交集靶點255個； KEGG通路富集結(jié)果顯示，關(guān)鍵靶點主要參與晚期糖基化終末產(chǎn)物及其受體（AGE/RAGE）信號通路、脂質(zhì)代謝異常導致的動脈粥樣硬化通路等多個與免疫反應和炎癥過程密切相關(guān)的信號通路。此外，分子對接研究表明，該方劑的主要化學成分對于AGE/RAGE信號通路上的主要靶點表現(xiàn)出良好的結(jié)合能力。細胞實驗結(jié)果表明，當歸補血湯能夠抵抗HK-2細胞經(jīng)高糖誘導產(chǎn)生的炎癥反應，并且能夠抑制AGE/RAGE信號通路上的核心蛋白表達。結(jié)論 當歸補血湯可能通過抑制AGE/RAGE信號通路，減輕高糖所致的炎癥反應，從而達到治療DN的目的，可為當歸補血湯深入研究提供方向。

Objective To investigate the mechanism of Danggui Buxue Decoction (DBD) against diabetic nephropathy (DN) based on network pharmacology, molecular docking and cell experiments. Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Traditional Chinese Medicine Integrated Database (TCMID) were used to screen the active components of Astragalus membranaceus and Angelica sinensis in DBD. Potential targets of these active compounds were identified using the UniProt and Swiss Target Prediction databases. Disease-related targets of DN were retrieved from GeneCards and OMIM. Protein-protein interaction (PPI) networks and a "drug-active component-target" network were constructed using the STRING database and visualized with Cytoscape. Functional enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, was performed using the DAVID database. The key findings were further validated through molecular docking and in vitro cell experiments. Results Network pharmacology analysis identified 32 active components in DBD and 255 overlapping targets associated with DN. KEGG pathway enrichment revealed that the core targets were primarily involved in the AGE/RAGE (advanced glycation end products/receptor for AGEs) signaling pathway, atherosclerosis pathways linked to lipid metabolism disorders, and other critical pathways related to immune response and inflammatory processes. Molecular docking studies demonstrated strong binding affinities between the major bioactive compounds of DBD and key targets in the AGE/RAGE pathway. In vitro experiments confirmed that DBD significantly attenuated high glucose-induced inflammatory responses in HK-2 cells and suppressed the expression of core proteins in the AGE/RAGE signaling pathway. Conclusion DBD may exert therapeutic effects against diabetic nephropathy by inhibiting the AGE/RAGE signaling pathway, thereby alleviating hyperglycemia-induced inflammation. These findings provide a scientific foundation for further research into the pharmacological mechanisms of DBD in DN treatment.

R285.5

江蘇省基礎研究計劃自然科學基金-前沿引領技術(shù)基礎研究專項（ BK20232014）