目的 探討芪參益氣滴丸對(duì)腹主動(dòng)脈縮窄大鼠的腎保護(hù)效應(yīng)和機(jī)制。方法 通過網(wǎng)絡(luò)藥理學(xué)篩選芪參益氣滴丸活性成分及腎損傷靶點(diǎn)，構(gòu)建“中藥-成分-靶點(diǎn)-疾病”網(wǎng)絡(luò)和蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)，并進(jìn)行分子對(duì)接；采用腹主動(dòng)脈縮窄復(fù)制壓力超負(fù)荷大鼠模型，隨機(jī)分為假手術(shù)組、模型組、纈沙坦組、芪參益氣滴丸組。藥物干預(yù)8周后檢測(cè)腎功能指標(biāo)、腎組織病理及纖維化標(biāo)志物變化。結(jié)果 篩選芪參益氣滴丸活性成分124個(gè)，藥物-疾病共同靶點(diǎn)203個(gè)；關(guān)鍵活性成分為槲皮素、木犀草素、山柰酚、丹參酮Ⅱ_A等，核心靶點(diǎn)為AKT1、TNF、IL-6等；基因本體（GO）注釋及京都基因與基因組百科全書（KEGG）通路富集分析顯示PI3K-Akt通路、AGE-RAGE、MAPK通路等是潛在的作用環(huán)節(jié)；分子對(duì)接證實(shí)丹參酮Ⅱ_A與核心靶點(diǎn)結(jié)合親和力強(qiáng)；與模型組比較，芪參益氣滴丸干預(yù)能夠降低腹主動(dòng)脈縮窄大鼠血清肌酐、尿素氮水平及24 h尿蛋白含量（P<0.05、0.01），顯著改善大鼠腎功能；腎臟膠原容積分?jǐn)?shù)亦明顯降低（P<0.01），且抑制轉(zhuǎn)化生長(zhǎng)因子β1（TGF-β1）、結(jié)締組織生長(zhǎng)因子（CTGF）蛋白表達(dá)（P<0.01），減輕腎纖維化。結(jié)論 芪參益氣滴丸具有多成分、通過多靶點(diǎn)、作用多環(huán)節(jié)發(fā)揮腎臟保護(hù)效應(yīng)，其機(jī)制可能與抑制TGF-β1、CTGF表達(dá)相關(guān)。

Objective To investigate the renoprotective effects and mechanisms of Qishen Yiqi Dropping Pills in rats with abdominal aortic constriction. Methods The active ingredients of Qishen Yiqi Dropping Pills and targets associated with kidney injury were screened using network pharmacology, which was also used to build “TCM-component-target-disease” networks, protein-protein interaction networks, and molecular docking; Abdominal aortic constriction was used to create a pressure overload rat model, which was then randomly assigned to four groups: sham operation, model, valsartan, Qishen Yiqi Dropping Pills, and. Renal function indicators, renal histology, and fibrosis markers were evaluated following an 8-week medication intervention. Results A total of 124 active components of Qishen Yiqi Dropping Pills were tested, and 203 common drug-disease targets were found. Key active components were quercetin, luteolin, kaempferol, and tanshinone Ⅱ_A, with main targets such as AKT1, TNF, and IL-6. GO functional and KEGG enrichment studies identified the PI3K-Akt, AGE-RAGE, and MAPK pathways as probable mechanisms of action. Molecular docking confirmed a significant binding affinity between tanshinone Ⅱ_A and the key targets. Qishen Yiqi Dropping Pills effectively lowered serum creatinine, blood urea nitrogen levels, and 24 h urine protein content in rats with abdominal aortic constriction（P＜0.05, 0.01）, leading to improved renal function. Renal collagen volume fraction decreased significantly（P＜0.01）, whereas TGF-β1 and CTGF protein expression were suppressed（P＜0.01）, resulting in reduced renal fibrosis. Conclusion Qishen Yiqi Dropping Pills exert renoprotective effects through multiple components acting on multiple targets and pathways, with mechanisms potentially related to inhibition of TGF-β1 and CTGF expression.

R285.5

國(guó)家自然科學(xué)基金項(xiàng)目(81603559); 蘇州工業(yè)園區(qū)東方華夏心血管健康研究院--力·心中藥科研創(chuàng)新基金項(xiàng)目(2024-CCATCM-005)