目的 基于網(wǎng)絡藥理學和靶向驗證探討木犀草素治療結腸癌的作用機制。方法 基于網(wǎng)絡藥理學篩選木犀草素治療結腸癌的潛在靶點，通過蛋白互作網(wǎng)絡進一步篩選核心靶點，基于核心靶點進行京都基因與基因組百科全書（KEGG）分析，找到關鍵的作用通路；根據(jù)找到的關鍵靶點及通路進行在體結腸癌移植瘤模型的藥理實驗驗證。采用ELISA試劑盒檢測關鍵指標的水平，采用蘇木精-伊紅（HE）染色評價藥物對腫瘤的病理學改變，采用免疫組織化學法及免疫印跡法檢測腫瘤關鍵靶蛋白的表達。結果 木犀草素可能主要作用于白細胞介素-6（IL-6）、白細胞介素-1β（IL-1β）、腫瘤壞死因子-α（TNF-α）等靶點，影響Toll樣受體（TLR）/髓樣分化因子88（MyD88）/核因子-κB（NF-κB）信號通路起到治療腫瘤的效果。實驗驗證結果顯示，木犀草素顯著降低了荷瘤小鼠機體的IL-6、IL-1β、TNF-α水平，改善了機體的氧化應激狀態(tài)[提升超氧化物歧化酶（SOD）水平，降低丙二醛（MDA）水平]，抑制了TLR/MyD88/NF-κB信號通路的表達。結論 木犀草素具有顯著的抗結腸癌效果，可能是通過降低機體炎癥水平、改善氧化應激狀態(tài)以及抑制TLR/MyD88/NF-κB通路表達實現(xiàn)的。

Objective To investigate the effect and mechanism of luteolin in treatment of colon cancer based on network pharmacology and targeted validation. Methods Potential targets of luteolin in treatment of colon cancer were screened based on network pharmacology, and the core targets were further screened by protein network interaction. KEGG analysis was performed based on the core targets to find the key pathways. According to the key targets and identified pathways, pharmacological experiments were carried out to verify in colon cancer model. ELISA kit was used to detect the content level of key indicators, HE staining was used to evaluate the pathological changes of the drug on the tumor. Immunohistochemistry and Western blotting were used to detect the expression of key target proteins of the tumor. Results Luteolin may mainly act on IL-6, IL-1β, TNF-α and affect TLR/MyD88/NF-κB signaling pathway to play a therapeutic effect on tumors. The experimental results showed that luteolin significantly reduced the level of IL-6, IL-1β, TNF-α, and improved the oxidative stress state (increasing SOD level, decreasing MDA level), and inhibited the expression of TLR/MyD88/NF-κB signaling pathway in tumor mice. Conclusion Luteolin has a significant anti-tumor effect on colon cancer, which may be achieved by reducing the level of inflammation, improving oxidative stress, and inhibiting TLR/MyD88/NF-κB.

R285

河南省醫(yī)學科技攻關計劃項目（2018020135）