目的 探討四逆散對重度抑郁癥、廣泛性焦慮癥和乳腺纖維囊性疾病“異病同治”的作用機制。方法 篩選四逆散活性成分，并與治療抑郁癥、焦慮癥和乳腺纖維囊性疾病的藥物進行主成分分析判斷類藥性；利用多個數(shù)據(jù)庫綜合分析四逆散和3種疾病的作用靶點，使用DAVID數(shù)據(jù)庫對共有靶點進行基因本體（GO）與京都基因與基因組百科全書（KEGG）通路分析，運用BioGPS數(shù)據(jù)庫對關鍵靶點進行定位分析。采用皮質酮（CORT）誘導PC12細胞制備抑郁癥、焦慮癥模型，6.250 0、3.125 0、1.562 5 mg·mL^-1四逆散干預處理，MTT檢測細胞存活率，實時熒光定量PCR（qRT-PCR）法檢測白細胞介素-1β（IL-1β）、白細胞介素-6（IL-6）mRNA表達。結果 四逆散主要活性成分具有較好的類藥性，四逆散“異病同治”共有靶點32個，關鍵靶點為IL6、腫瘤壞死因子（TNF）、細胞腫瘤抗原p53（TP53）、絲氨酸/蘇氨酸激酶1（AKT1）和IL1B等，關鍵活性成分包括槲皮素、木犀草素和川陳皮素等。四逆散主要通過調控HIF-1、癌癥和PI3K-Akt等多條信號通路發(fā)揮“異病同治”功能，推測肝、胸腺是藥物發(fā)揮作用的關鍵部位。實驗結果顯示四逆散可逆轉CORT對PC12的細胞毒性，影響不同時間點IL-1β、IL-6 mRNA表達。結論 四逆散具有“多成分、多靶點、多通路”協(xié)同作用的特點，通過調節(jié)炎癥反應等發(fā)揮“異病同治”作用。

Objective To investigate the mechanism of Sini Powder in treatment of major depressive disorder, generalized anxiety disorder, breast fibrocystic disease with the "homotherapy for heteropathy". Methods The active components of Sini Powder were screened and compared the drug-like properties with existing drugs for the treatment of major depressive disorder, generalized anxiety disorder, breast fibrocystic disease using principal component analysis. Multiple databases were used to analyze the targets of Sini Powder and three diseases, DAVID database was used to conduct GO enrichment and KEGG pathway analysis of common targets, BioGPS database was used to locate and analyze the key targets. Corticosterone (CORT) induced PC12 cells was used to prepare models of depression. Sini Powder (6.250 0, 3.125 0, 1.562 5 mg·mL^-1) was used for intervention treatment. Cell survival was detected by MTT, IL-1β and IL-6 mRNA expression was tested by qRT-PCR. Results Most of the active components of Sini Powder had good drug-like properties. There were 32 common targets of Sini Powder treating three diseases with "homotherapy for heteropathy". The key targets were IL6, TNF, TP53, AKT1 and IL1B, etc. The key active components were quercetin, luteolin, and nobiletin, etc. Sini Powder mainly played the role of treating different diseases through HIF-1, pathways in cancer and PI3K-Akt signaling pathway. It was speculated that the liver and thymus were the key parts of the drug. The results of cell experiments showed that Sini Powder could reverse the cytotoxicity of CORT on PC12 and affected the mRNA expression of IL-1β and IL-6. Conclusion The treatment of three diseases with Sini Powder reflected the thought of "homotherapy for heteropathy" in Chinese medicine through multiple components, multiple targets, and multiple pathways by regulating inflammatory response and other factors.

R285.5

山西省基礎研究計劃青年科學研究項目（202203021222278）;山西省高等學校科技創(chuàng)新項目（2020L0420）;山西中醫(yī)藥大學科技創(chuàng)新能力培育計劃“基礎研究專項”項目（2020PY-JC-06）*通信作者：胡麗麗，女，博士，副教授，研究方向為中藥抗炎。E-mail：hulili0204@163.com