目的 优化安神定志丸（Anshen Dingzhi Pills，ADP）的制备工艺参数，并探究其对睡眠剥夺模型大鼠认知障碍的药效作用。方法 以蜂蜜与药粉比例、干燥时间、干燥温度进行单因素考察，以外观性状、溶散时限及6个指标性成分（远志𠮿酮III、3,6′-二芥子酰基蔗糖、人参皂苷Rb₁、β-细辛醚、去氢土莫酸、茯苓酸）作为综合评价指标，运用AHP-熵权法（entropy weight method）结合Box-Behnken设计-响应面法（Box-Behnken design-response surface method，BBD-RSM）优选ADP最佳制备工艺参数。同时，采用改良多平台水环境法诱导睡眠剥夺大鼠模型，系统评价ADP对睡眠剥夺模型大鼠运动与学习记忆能力、海马组织病理、血清中炎症因子肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-1β（interleukin-1β，IL-1β）和IL-6及脑组织中氧化应激指标超氧化物歧化酶（superoxide dismutase，SOD）、还原型谷胱甘肽（glutathione，GSH）和丙二醛水平的影响。结果 ADP最佳制备工艺参数为蜂蜜与药粉比例0.316∶1，干燥时间14.0 h，干燥温度50 ℃。药效研究结果表明，制备的ADP显著缩短了睡眠剥夺大鼠的逃避潜伏期，增加了穿越平台的次数、目标象限活动时间和新物体识别指数；显著减轻了模型大鼠脑组织海马CA1区神经元细胞结构损伤；降低了血清中炎症因子（TNF-α、IL-1β和IL-6）水平，有效调节了脑组织中氧化应激（SOD、GSH和丙二醛）表达水平。结论 优化所得的ADP制备工艺稳定且质量均一，能够显著改善睡眠剥夺大鼠的认知功能和海马神经细胞形态，降低炎症因子水平，减轻氧化应激损伤，也可为ADP的制剂开发和临床应用提供了科学参考依据。

Objective To optimize the preparation process parameters of Anshen Dingzhi Pills (ADP, 安神定志丸) and explore its efficacy in alleviating cognitive impairment in sleep deprived model rats. Methods Single factor experiments were conducted on the ratio of powder to honey, drying time and drying temperature. The appearance characteristics, disintegration time limit and six index components (polygalaxanthone III, 3,6′-disinapoylsucrose, ginsenoside Rb₁, β-asarone, dehydrotumulosic acid and pachymic acid) were used as comprehensive evaluation indexes. The AHP-entropy weight method combined with the Box-Behnken design-response surface method (BBD-RSM) were used to optimize the best process parameters for the preparation of ADP. The improved multi-platform water environment method was used to induce a rat model of sleep deprivation. The efficacy of ADP on sleep deprivation rats with cognitive impairment was evaluated by motor function, learning and memory performance, hippocampal histopathological changes, serum levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 and oxidative stress markers in brain tissue, such as superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA). Results The optimal preparation process parameters for ADP was determined as follows, the ratio of honey to medicinal powder of 0.316:1, drying time of 14.0 h and drying temperature of 50 ℃. Pharmacological evaluation demonstrated that the prepared ADP significantly reduced escape latency in sleep deprived rats, increased the number of platform crossings, time spent in the target quadrant, and novel object recognition index. Additionally, it markedly alleviated neuronal structural damage in the hippocampal CA1 region, decreased serum levels of inflammatory factors (TNF-α, IL-1β and IL-6) and effectively regulated the expression levels of oxidative stress (SOD, GSH and MDA) in brain tissue. Conclusion The optimized ADP preparation process is stable and has consistent quality, which can significantly improve the cognitive function and hippocampal nerve cell morphology of sleep-deprived rats, reduce the levels of inflammatory factors, alleviate oxidative stress damage, and also provide a scientific reference basis for the development of ADP preparations and clinical applications.

R283.6

合肥综合性国家科学中心大健康研究院新安医学与中医药现代化研究所“揭榜挂帅”项目（2023CXMMTCM014）；安徽省自然基金项目（2408085MH229）；安徽省科技重大专项项目（202203a07020031）