[關(guān)鍵詞]
[摘要]
目的 系統(tǒng)整理并歸納總結(jié)阿爾茨海默?。ˋD)的中藥復(fù)方臨床用藥規(guī)律及特點,研究核心中藥的潛在作用機制。方法 通過檢索中國學(xué)術(shù)期刊全文數(shù)據(jù)庫(CNKI)、萬方數(shù)據(jù)庫(Wanfang Data)、維普生物醫(yī)學(xué)數(shù)據(jù)庫(VIP)、中國生物醫(yī)學(xué)文獻數(shù)據(jù)庫(SinoMed)、EMbase、PubMed、Cochrane Library和Web of Science數(shù)據(jù)庫自建庫至2024年4月中藥復(fù)方治療AD的臨床研究,篩選數(shù)據(jù)并使用Excel建立數(shù)據(jù)庫。運用R Studio軟件進行中藥頻次、頻率、劑量、功效、性味、歸經(jīng)、關(guān)聯(lián)規(guī)則和層次聚類的分析。利用網(wǎng)絡(luò)藥理學(xué)方法預(yù)測核心中藥的潛在作用靶點和通路,從TCMSP數(shù)據(jù)庫和OMIM等數(shù)據(jù)庫中分別獲取中藥與AD相關(guān)的靶點,取交集靶點后上傳至STRING數(shù)據(jù)庫構(gòu)建蛋白質(zhì)-蛋白質(zhì)相互作用(PPI)網(wǎng)絡(luò),將結(jié)果導(dǎo)入Cytoscape 3.9.1軟件中,運用CytoNCA工具計算網(wǎng)絡(luò)拓?fù)鋮?shù)并得到關(guān)鍵靶點,并進行基因本體(GO)和京都基因與基因組百科全書(KEGG)通路富集分析。結(jié)果 在納入的131首方劑中,中藥頻次以石菖蒲、熟地黃和川芎應(yīng)用最廣。中藥功效前3名分別為補虛藥、活血化瘀藥和安神藥。中藥四性以溫、平居多,五味中甘、苦、辛味為主,歸經(jīng)中以肝、腎和心為主。關(guān)聯(lián)規(guī)則分析中支持度≥12%、置信度≥80%時,共得到關(guān)聯(lián)規(guī)則19條。高頻中藥聚類分析得到6類中藥。核心中藥石菖蒲、熟地黃和川芎與AD的交集靶點124個,經(jīng)拓?fù)鋵W(xué)分析得到其治療AD的8個關(guān)鍵靶點,包括絲氨酸/蘇氨酸激酶1(AKT1)、腫瘤壞死因子(TNF)、Jun原癌基因(JUN)等。KEGG分析結(jié)果提示主要涉及神經(jīng)營養(yǎng)因子(neurotrophin)、AD、C型凝集素受體(C-type lectin receptor)等信號通路。結(jié)論 該研究總結(jié)歸納了中藥復(fù)方治療AD的用藥規(guī)律,用藥以補益肝腎、活血化瘀和化痰開竅為主。揭示了核心中藥通過不同通路治療AD的多種機制,為后續(xù)中藥復(fù)方臨床用藥和科學(xué)研究提供參考。
[Key word]
[Abstract]
Objective To systematically review and summarize the clinical application patterns and characteristics of traditional Chinese medicine (TCM) formulas in the treatment of Alzheimer's disease (AD) and to investigate the potential mechanisms of action of core Chinese herbs.Methods A comprehensive literature search was conducted in CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, Cochrane Library, and Web of Science for clinical studies on TCM formulas for AD from database inception to April 2024. Data were screened and compiled into a database using Excel. R Studio software was employed to analyze the frequency, dose, efficacy, properties, meridian tropism, association rules, and hierarchical clustering of the included Chinese herbs. Network pharmacology was used to predict the potential targets and pathways of core Chinese herbs. Targets related to both the selected herbs and AD were obtained from the TCMSP and OMIM databases, and their intersection was uploaded to the STRING database to construct a protein-protein interaction (PPI) network. The results were then imported into Cytoscape 3.9.1, and key targets were identified through network topology analysis using the CytoNCA tool. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed.Results Among the 131 included formulas, Acorus Tatarinowii, Rehmannia glutinosai, and Ligusticum chuanxiong were the most frequently used herbs. The three most common therapeutic effects were tonifying deficiency, promoting blood circulation and removing blood stasis, and calming the mind. In terms of the four natures of Chinese medicine, warm and neutral properties were predominant, while the five flavors were mainly sweet, bitter, and pungent. The primary meridian tropisms were the liver, kidney, and heart. Association rule analysis identified 19 rules with a support threshold o f ≥ 12% and a confidence level of ≥80%. High-frequency herbs were clustered into six categories. A total of 124 overlapping targets were identified for the core Chinese herbs (Acorus Tatarinowii, Rehmannia glutinosai, and Ligusticum chuanxiong) in AD treatment, with eight key targets determined through topological analysis, including serine/threonine kinase 1 (AKT1), tumor necrosis factor (TNF), and Jun proto-oncogene (JUN). KEGG pathway analysis indicated that the primary signaling pathways involved neurotrophin, Alzheimer's disease, and C-type lectin receptor pathways.Conclusion This study systematically summarizes the therapeutic patterns of TCM formulas for AD, with an emphasis on tonifying the liver and kidney, promoting blood circulation to remove blood stasis, and resolving phlegm to open orifices. It elucidates the multiple mechanisms by whi ch core Chinese herbs exert therapeutic effects through different pathways, providing valuable references for future clinical applications and scientific research on TCM formulas for AD.
[中圖分類號]
R285.5
[基金項目]
國家自然科學(xué)基金面上項目(82274616);廣東省基礎(chǔ)與應(yīng)用基礎(chǔ)研究基金企業(yè)聯(lián)合基金項目(2022A1515220121)