目的 制備并表征黃芪多糖-皂苷納米聚集體（APS-AST-NPs），探究其對心腎共損傷模型小鼠的保護作用。方法 采用37℃恒溫水浴制備APS-AST-NPs，通過粒徑、紫外-可見光譜（UV-Vis）、傅里葉變換紅外光譜（FT-IR）和透射電子顯微鏡（TEM）進行理化表征；采用高效液相-質(zhì)譜（HPLC-MS）聯(lián)用技術(shù)鑒定皂苷類成分，通過酸水解結(jié)合1-苯基-3-甲基-5-吡唑啉酮（PMP）柱前衍生化，利用HPLC分析多糖單糖組成。通過心腎共損傷模型小鼠干預(yù)實驗進行藥效評價：采用ELISA法檢測血清氨基末端腦鈉肽前體（NT-proBNP）、胱抑素C (Cys-C)、血清尿素氮（BUN）及微量白蛋白（m ALB）水平；利用小動物心臟超聲儀評估心臟功能相關(guān)參數(shù)，包括左室射血分?jǐn)?shù)（LVEF）、左心室縮短分?jǐn)?shù)（LVFS）、心率（HR）、心輸出量（CO）、左心室前后壁舒張/收縮末期厚度（LVAWd、LVAWs、LVPWd、LVPWs）及左心室舒張末期容積（LVEDV）、左心室收縮末期容積（LVESV）。結(jié)果 綜合表征結(jié)果證實，APS與AST可自組裝形成APS-AST-NPs;HPLC-MS分析鑒定出19種皂苷類成分；APS-AST-NPs的單糖組成包括葡萄糖（81.09%）、鼠李糖（7.48%）、葡萄糖醛酸（6.37%）、半乳糖（1.53%）和阿拉伯糖（3.53%）。藥效結(jié)果顯示，與模型組相比，APS-AST-NPs可顯著增加小鼠體質(zhì)量（P<0.05），并有效改善心臟功能：LVEF、LVFS、HR、CO顯著升高（P<0.01、0.001），而LVAWs和LVAWd顯著降低（P<0.05）；同時，血清中心腎損傷標(biāo)志物NT-proBNP、Cys-C及BUN水平顯著降低，腎功能保護指標(biāo)mALB水平顯著升高（P<0.05、0.001），提示APSAST-NPs對心腎損傷均具有顯著改善作用。結(jié)論 證實APS-AST-NPs對心腎共損傷小鼠的心腎功能具有明確的保護作用，為心腎共損傷的臨床治療策略優(yōu)化及相關(guān)納米制劑研發(fā)提供了重要實驗依據(jù)。

Objective To prepare and characterize Astragalus polysaccharide-saponins nanocomplexes（APS-AST-NPs） and explore its protective effects on mice with co-injury of heart and kidney. Methods APS-AST-NPs were prepared by a 37 ℃ constant temperature water bath. Multi-scale physicochemical characterization was conducted by particle size, UV-Vis, FT-IR and TEM. Saponin components were identified by HPLC-MS. The monosaccharide composition of polysaccharides was analyzed by HPLC after acid hydrolysis combined with 1-phenyl-3-methyl-5-pyrazolone（PMP） pre-column derivatization. The efficacy was evaluated by intervention experiments in mice with co-injury of heart and kidney: serum levels of N-terminal pro-brain natriuretic peptide（NTproBNP）, cystatin C（Cys-C）, blood urea nitrogen（BUN） and microalbumin（mALB） were detected by ELISA; cardiac function parameters including left ventricular ejection fraction（LVEF）, left ventricular fractional shortening（LVFS）, heart rate（HR）, cardiac output（CO）, left ventricular anterior and posterior wall thickness at end-diastole and end-systole（LVAWd, LVAWs, LVPWd, LVPWs）, left ventricular end-diastolic volume（LVEDV） and left ventricular end-systolic volume（LVESV） were evaluated by small animal echocardiography. Results Comprehensive characterization results confirmed that APS and AST could self-assemble to form APSAST-NPs; 19 saponin components were identified by HPLC-MS; the monosaccharide composition of APS-AST-NPs included glucose（81.09%）, rhamnose（7.48%）, glucuronic acid（6.37%）, galactose（1.53%） and arabinose（3.53%）. Efficacy results showed that compared with the model group, APS-AST-NPs significantly increased the body weight of mice（P＜0.05）, and effectively improved cardiac function: LVEF, LVFS, HR and CO significantly increased（P＜0.01, 0.001）, while LVAWs, LVAWd significantly decreases（P＜0.05）; at the same time, the levels of serum markers of heart and kidney injury NT-proBNP, Cys-C and BUN significantly decreased, and the level of renal function protection index mALB significantly increased（P＜0.05, 0.001）, suggesting that APS-ASTNPs have significant improvement effects on heart and kidney injury. Conclusion It was confirmed that APS-AST-NPs have a clear synergistic protective effect on the heart and kidney function of mice with co-injury of heart and kidney, providing important experimental basis for the optimization of clinical treatment strategies for co-injury of heart and kidney and the development of related nanomedicines.

R944.9

國家自然科學(xué)基金資助項目(82204595);國家自然科學(xué)基金項目聯(lián)合基金資助項目(U23A20517); 山西省基礎(chǔ)研究計劃資助項目(202303021221070); 中國博士后基金資助項目(340903); 山西省中醫(yī)藥科技創(chuàng)新工程資助項目(2025kjzy006); 山西省“三晉英才”科技創(chuàng)新領(lǐng)域青年拔尖人才項目