目的 探究中药治疗记忆障碍的配伍特点及用药规律，为中医药临床治疗记忆障碍类疾病及药物研发提供理论支持和参考。方法 以“呆病”“痴呆”“呆证”“健忘”及“喜忘”为关键词检索华柄方剂大数据2.0（数据挖掘版）、药智数据库、中国知网、维普、万方等数据库，收集治疗记忆障碍的相关方剂。对目标方剂的中药性味归经、用药频次等进行统计分析，并通过关联规则分析探究中药复方治疗记忆障碍的配伍特点。对得出的核心方剂七福饮拆方为五福饮、远志-酸枣仁，并采用网络药理学与动物实验相结合方法进行配伍分析。结果 共收集到425首治疗记忆障碍的目标方剂，涉及中药220味，使用频次排名前10的中药为远志、茯苓、当归、石菖蒲、人参、黄芪、熟地黄、酸枣仁、川芎、白术，除人参外，这些中药的主要用量均在《中国药典》2020年版范围内。药物的药性以温性为主，占46.58%；药味以甘味居多，占39.66%；药物归经以肝、心、脾经为主，分别占比18.22%、18.00%和16.47%；补虚类中药占比37.05%。“远志-石菖蒲”和“远志-茯苓”为高频药对，在治疗记忆障碍中药方剂的关联药物中，其核心药物组成为七福饮。网络药理学分析筛选得到81种活性成分，其中五福饮中的成分有62种，远志-酸枣仁中的成分有19种，主要为黄酮、皂苷、环烯醚萜和挥发油类成分，成分涉及作用靶点634个，筛选得到疾病靶点1 471个。成分和疾病交集靶点68个，主要核心靶点为信号转导和转录激活因子3（signal transducer and activator of transcription 3，STAT3）、淀粉样前体蛋白（amyloid precursor protein，APP）、基质金属蛋白酶9（matrix metalloproteinase 9，MMP9）等。京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析主要涉及Calcium信号通路等。Morris水迷宫行为学实验表明，七福饮、五福饮和远志-酸枣仁均能够显著增加模型小鼠进入目标象限平台的次数、运动距离、停留时间。免疫组化实验结果表明，七福饮、五福饮与酸枣仁-远志可以明显降低脑组织中钙调蛋白（calmodulin，CaM）的水平。结论 记忆障碍的病机本虚标实，本虚多为肝、心、脾、肾之亏虚，用药以补虚药居多，重在补其本。常用七福饮等经典方加减治疗记忆障碍。治疗记忆障碍的方剂组方配伍强调疾病和辨证相结合，并根据其不同病因采取不同的治疗方法。

Objective To explore the compatibility characteristics and medication rules of traditional Chinese medicine (TCM) in the treatment of memory disorders, and provide theoretical support and reference for the clinical treatment of memory disorders and drug research and development. Methods Using “dementia”, “dementia syndrome”, “forgetfulness” and “happiness forgetting” as keywords, the Huabing prescription Big Data 2.0 (data mining version) and Yaozhi database, China National Knowledge Network, VIP, Wanfang and other databases were searched to collect the relevant TCM prescriptions in the treatment of memory disorders. Statistical analysis was made on the TCM nature, flavor, channel and the frequency of administration of the target prescription, and the compatibility characteristics of TCM compound in the treatment of memory disorders were explored through association rule analysis. The core prescription Qifu Yin (七福饮) was obtained, and the disassembled prescriptions were Wufu Yin (五福饮) and Yuanzhi (Polygalae Radix)-Suanzaoren (Ziziphi Spinosae Semen), and the compatibility analysis was carried out by combining network pharmacology with animal experimental. Results A total of 425 target prescriptions for memory disorders were collected, involving 220 TCMs. The top 10 most frequently used TCMs were Polygalae Radix, Fuling (Poria), Danggui (Angelicae Sinensis Radix), Shichangpu (Acori Tatarinowii Rhizoma), Renshen (Ginseng Radix et Rhizoma), Huangqi (Astragali Radix), Shudihuang (Rehmanniae Radix Praeparata), Ziziphi Spinosae Semen, Chuangxiong (Chuanxiong Rhizoma), Baizhu (Atractylodis Macrocephalae Rhizoma). In addition to Ginseng Radix et Rhizoma, the main dosage of these Chinese medicines is within the scope of the 2020 edition of the Chinese Pharmacopoeia. The medicinal properties of drugs are mainly warm, accounting for 46.58%. The medicinal taste is mainly sweet, accounting for 39.66%. The main meridians for drugs are liver, heart, and spleen, accounting for 18.22%, 18.00%, and 16.47%, respectively. TCM for tonifying deficiency accounts for 37.05%. Analysis shows that “Polygalae Radix-Acori Tatarinowii Rhizoma” and “Polygalae Radix-Poria” are high-frequency drug pairs. Among the associated drugs in TCM formulas for treating memory disorders, the core drug composition is Qifu Yin. A total of 81 active components were screened by network pharmacology analysis, including 62 components in Wufu Yin, 19 components in Polygalae Radix-Ziziphi Spinosae Semen, mainly components of flavonoids, saponins, iridoids and volatile oil. The components involved 634 action targets, and 1 471 disease targets were screened. There were 68 intersection targets of components and diseases, and the main core targets were signal transducer and signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), matrix metalloproteinase 9 (MMP9), etc. Pathway enrichment analysis of Kyoto encyclopedia of genes and genomes (KEGG) mainly involved calcium signaling pathways. Morris water maze behavioral experiments showed that the number of times, distance and residence time of mice entering the target quadrant platform were significantly increased after administration of Qifu Yin, Wufu Yin and Polygalae Radix-Ziziphi Spinosae Semen. The results of immunohistochemistry showed that the administration of Qifu Yin, Wufu Yin and Polygalae Radix-Ziziphi Spinosae Semen could reduce the level of calmodulin (CaM) in brain tissue. Conclusion The pathological nature of memory impairment is characterized by deficiency of the liver, heart, spleen, and kidney. The main focus of medication is to supplement the deficiency of the liver, heart, spleen, and kidney. Commonly used classic formulas such as Qifu Yin are modified to treat memory disorders. The prescription for treating memory impairment is flexible, with exquisite compatibility, emphasizing the combination of disease and syndrome differentiation and adopting different treatment methods according to their causes.

R285

国家中医药管理局李冀名老中医药专家传承工作室项目(2014);山西中医药大学科技创新能力培育计划“太行本草”项目(2022PY-TH-15)