目的 通過網(wǎng)絡(luò)藥理學(xué)分析及相關(guān)的動(dòng)物實(shí)驗(yàn)探討黃芪六一湯藥效組分（HQD）調(diào)控腎小管上皮細(xì)胞自噬水平抗糖尿病腎?。―N）的機(jī)制。方法 采用 DN 大鼠模型考察 HQD 抗 DN 的作用。利用 SwissTargetPrediction 數(shù)據(jù)庫獲得 HQD 主要入血成分的相關(guān)靶點(diǎn)，并與 GeneCard、DisGeNET 和 OMIM 數(shù)據(jù)庫中篩選的疾病靶點(diǎn)取交集；利用 STRING 數(shù)據(jù)庫和Cytoscape 構(gòu)建蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)獲得核心靶點(diǎn)；采用 Metascape 數(shù)據(jù)庫對(duì)交集靶點(diǎn)進(jìn)行基因本體（GO）注釋及京都基因與基因組百科全書（KEGG）通路富集分析。利用 DN 大鼠模型對(duì)預(yù)測(cè)結(jié)果進(jìn)行驗(yàn)證。結(jié)果 與對(duì)照組比較，HQD 能顯著降低 DN 模型大鼠血糖（FBG）、血肌酐（Scr）、尿素氮（BUN）、總膽固醇（TC）、三酰甘油（TG）、低密度脂蛋白（LDL）、24 h 尿白蛋白（24 h-U-Alb）值（P＜0.05），抑制腎組織細(xì)胞凋亡（P＜0.05）。網(wǎng)絡(luò)藥理學(xué)研究顯示 HQD 主要通過 STAT3、EGFR、VEGFA、JUN、TNF、AKT1、CASP3、mTOR、IL2 等關(guān)鍵靶點(diǎn)，作用于癌癥通路、癌癥中的蛋白多糖、PI3K-Akt 信號(hào)通路、MAPK 等信號(hào)通路；動(dòng)物驗(yàn)證實(shí)驗(yàn)顯示 HQD 能下調(diào) PI3K/Akt/mTOR 信號(hào)通路相關(guān)蛋白的表達(dá)，上調(diào)腎臟組織自噬相關(guān)蛋白 Beclin-1、LC3Ⅱ/Ⅰ的表達(dá)（P＜0.05），增加腎小管上皮細(xì)胞自噬體及自噬溶酶體數(shù)量。結(jié)論 HQD 抗 DN 的分子機(jī)制可能與抑制 PI3K/Akt/mTOR 信號(hào)通路激活，促進(jìn)腎小管上皮細(xì)胞自噬水平，抑制細(xì)胞凋亡，減輕腎小管上皮細(xì)胞損傷有關(guān)。

Objective To investigate the mechanism by which the pharmacological component of Huangqi Liuyi Decocotion (HQD) modulates the level of autophagy in renal tubular epithelial cells against diabetic nephropathy (DN) through network pharmacological analysis and related animal experiments. Methods A rat model of DN was used to investigate the anti-diabetic nephropathy effect of HQD. The SwissTargetPrediction database was used to obtain the relevant targets of HQD's major blood-entry components and intersected with the disease targets screened in GeneCard, DisGeNET and OMIM databases; the STRING database and Cytoscape were used to construct a protein-protein interaction (PPI) network to obtain the core targets; Metascape database was used to analyze the GO and KEGG enrichment of the intersected targets. The predicted results were then validated using a diabetic nephropathy rat model. Results HQD significantly reduced blood glucose (FBG), blood creatinine (Scr), urea nitrogen (BUN), total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein (LDL), and 24 h urinary albumin (24 h-U-Alb) values in rats with DN (P<0.05), and inhibited apoptosis of renal tissue cells (P<0.05). Network pharmacological studies showed that HQD mainly acted on the cancer pathway, proteoglycans in cancer, PI3K-Akt signaling pathway, MAPK and other signaling pathways through key targets such as STAT3, EGFR, VEGFA, JUN, TNF, AKT1, CASP3, mTOR, IL2, etc. Animal validation experiments showed that HQD could down-regulate PI3K/Akt/mTOR signaling pathway-related proteins, up-regulate the expression of autophagy-related proteins Beclin-1 and LC3II/Ⅰ in renal tissues (P<0.05), and increase the number of autophagosomes and autophagic lysosomes in renal tubular epithelial cells.Conclusion The molecular mechanism of HQD against DN may be related to the inhibition of PI3K/ Akt/mTOR signaling pathway activation, promotion of autophagy level in renal tubular epithelial cells, inhibition of apoptosis, and attenuation of renal tubular epithelial cell injury.

R285.5

貴州省科技計(jì)劃項(xiàng)目（黔科合基礎(chǔ)-ZK［2023］一般 416）；2023 年度貴州中醫(yī)藥大學(xué)學(xué)術(shù)新苗項(xiàng)目（貴科合學(xué)術(shù)新苗［2023］-13號(hào)）；貴州省衛(wèi)生健康委科學(xué)技術(shù)基金項(xiàng)目（黔衛(wèi)健函［2024］24 號(hào)）；貴州中醫(yī)藥大學(xué)藥用高分子材料研究中心（貴中醫(yī) ZX 合字［2024］071 號(hào)）