目的 制备金丝桃苷-玉米肽纳米复合物（Hyp-CP-NCs），考察理化性质及其对肾脏缺血再灌注所致肾损伤的改善作用。方法 采用分子对接分析金丝桃苷与玉米肽的结合趋势；通过单因素实验结合Box?Behnken设计?效应面法优化制备工艺；利用透射电镜、X?射线粉末衍射、差式扫描量热、傅里叶变换红外光谱等技术表征复合物；测定其饱和溶解度与体外累积释放度；构建小鼠肾缺血再灌注模型，设置假手术、模型、缬沙坦(阳性药，10 mg·kg^-1)、金丝桃苷(120 mg·kg^-1)及Hyp?CP?NCs低、高剂量(60、120 mg·kg^-1)组，检测肾脏指数、血清肌酐（Scr）、尿素氮（BUN）水平，并观察肾组织病理变化。结果 优化后最佳工艺为玉米肽质量浓度13.66 mg·mL^-1、制备温度65℃、制备时间35 min；复合物包封率（84.02±0.80）%、载药量（5.19±0.07）%、粒径（70.64±4.13）nm，呈类球形，金丝桃苷以无定形态存在且与玉米肽以氢键结合；复合物显著提升金丝桃苷溶解度与体外释放度，18 h累积释放度达87.85%；动物实验显示，Hyp?CP?NCs可显著降低肾脏指数、血清Scr及BUN水平，明显改善肾小管萎缩、炎性浸润与胶原沉积，效果优于单用金丝桃苷。结论 Hyp?CP?NCs可有效改善金丝桃苷的溶解度与释放度，显著减轻肾脏缺血再灌注损伤，具备良好的开发前景。

Objective To prepare hyperoside-corn peptide nanocomplex（Hyp-CP-NCs） and investigate its physicochemical properties and its therapeutic effect on renal ischemia-reperfusion-induced renal injury. Methods Molecular docking analysis was conducted to explore the binding trend between hyperoside and corn peptide; single-factor experiments combined with Box-Behnken design-effect surface method were used to optimize the preparation process; transmission electron microscopy, X-ray powder diffraction, differential scanning calorimetry, and fourier transform infrared spectroscopy were employed to characterize the complex; the saturated solubility and in vitro cumulative release rate of the complex were determined; a mouse renal ischemia-reperfusion model was constructed, with sham operation, model group, valsartan(positive drug, 10 mg·kg^-1), Hyperoside(120 mg·kg^-1), and Hyp-CP-NCs at low and high doses(60, 120 mg·kg^-1) groups were set up. Renal index, serum creatinine, and urea nitrogen levels were measured, and renal tissue pathological changes were observed. Results The optimized best process was a corn peptide concentration of 13.66 mg·kg^-1, a preparation temperature of 65 ℃, and a preparation time of 35 min; the encapsulation rate of the complex was（84.02 ± 0.80）%, the drug loading was（5.19 ± 0.07）%, the particle size was（70.64 ± 4.13） nm, presenting a spheroidal shape, hyperoside existed in an amorphous form and was bound to corn peptide by hydrogen bonds; the complex significantly enhanced the solubility and in vitro release rate of hyperoside, with a cumulative release rate of 87.85% at 18 h; animal experiments showed that Hyp-CP-NCs could significantly reduce renal index, serum creatinine, and urea nitrogen levels, significantly improve renal tubular atrophy, inflammatory infiltration, and collagen deposition, and the effect was better than that of using hyperoside alone. Conclusion Hyp-CP-NCs can effectively improve the solubility and release rate of hyperoside, significantly alleviate renal ischemia-reperfusion injury, and have a promising development prospect.

R285.5

河南省科技攻关项目(252102230104); 河南省高等学校重点科研项目(23B310010)