目的 制备淫羊藿次苷II纳米乳（icariside II nanoemulsion，NE-ICS II），以提升口服生物利用度并增强抗脑缺血再灌注损伤（cerebral ischemia-reperfusion injury，CIRI）的能力。方法 采用超声乳化法制备NE-ICS II，并对其理化性质进行表征；系统评价药动学参数及脑内药物分布；通过在大脑中动脉闭塞（middle cerebral artery occlusion，MCAO）模型大鼠中检测脑梗死体积、神经功能评分、氧化应激及炎症指标评估其疗效；结合RNA测序解析其作用机制。结果 NE-ICS II的平均粒径为（147.59±0.71）nm，包封率为（84.85±5.47）%，可使ICS II的口服生物利用度提高2.4倍，显著增加药物在脑部的蓄积。治疗性口服NE-ICS II明显改善MCAO大鼠的神经功能，缩小脑梗死体积，减轻病灶氧化应激和炎症反应；RNA测序揭示其可能下调氧化应激与炎症相关信号通路。结论 NE-ICS II显著提升了ICS II的口服生物利用度，在低剂量下即可实现对CIRI的有效治疗，为实现ICS II的高效脑递送及中枢神经系统疾病的治疗提供新策略。

Objective To develop an icariside II nanoemulsion (NE-ICS II) to enhance oral bioavailability and improve efficacy against cerebral ischemia-reperfusion injury (CIRI). Methods NE-ICS II was prepared by ultrasonic emulsification and its physicochemical properties were characterized. Pharmacokinetic parameters and brain distribution were systematically evaluated. Therapeutic efficacy was assessed in rats subjected to middle cerebral artery occlusion (MCAO) by measuring infarct volume, neurological deficit scores, and oxidative stress and inflammatory markers. RNA sequencing was performed to elucidate the underlying mechanisms. Results NE-ICS II showed a mean particle size of (147.59 ± 0.71) nm and an encapsulation efficiency of (84.85 ± 5.47) %. NE-ICS II increased the oral bioavailability of ICS II by 2.4-fold and significantly enhanced its accumulation in the brain. Therapeutic oral administration of NE-ICS II markedly improved neurological function, reduced infarct volume, and attenuated oxidative stress and inflammatory responses in MCAO rats. RNA sequencing revealed that NE-ICS II may downregulate signaling pathways associated with oxidative stress and inflammation. Conclusion NE-ICS II substantially improves the oral bioavailability of ICS II and enables effective treatment of CIRI at a low dose, providing a promising strategy for efficient brain delivery of ICS II and for the treatment of central nervous system diseases.

R283.6

中国科协青年人才托举工程（GASTYESS202420）；遵义医科大学未来科技菁英人才项目（ZYSE-2022-02）；贵州省科技重大专项（ZKHHZ[2022]412）