目的 探討芹菜素調(diào)控動(dòng)脈粥樣硬化的作用及其潛在作用靶點(diǎn)。方法 將32只ApoE^-/-小鼠隨機(jī)分為對(duì)照組、模型組和芹菜素低、高劑量（10、30 mg·kg^-1）組，通過(guò)高膽固醇飼料喂養(yǎng)建立動(dòng)脈粥樣硬化模型。實(shí)驗(yàn)動(dòng)物飼養(yǎng)70 d后，分離各組實(shí)驗(yàn)動(dòng)物血管（主動(dòng)脈根部至胸主動(dòng)脈）并進(jìn)行油紅O染色，同時(shí)應(yīng)用蘇木精-伊紅（HE）染色檢測(cè)血管及主動(dòng)脈瓣斑塊。酶聯(lián)免疫吸附（ELISA）法檢測(cè)血清中總膽固醇（TC）、三酰甘油（TG）、高密度脂蛋白-膽固醇（HDL-C）和低密度脂蛋白-膽固醇（LDL-C）。使用網(wǎng)絡(luò)藥理學(xué)方法篩選芹菜素的靶點(diǎn)，并結(jié)合基因表達(dá)數(shù)據(jù)進(jìn)行差異分析，確定關(guān)鍵基因。通過(guò)單細(xì)胞轉(zhuǎn)錄組學(xué)分析關(guān)鍵基因在不同細(xì)胞類型中的表達(dá)，并使用分子對(duì)接技術(shù)驗(yàn)證芹菜素與關(guān)鍵基因的結(jié)合活性。結(jié)果與模型組相比，芹菜素具有抑制血管壁脂質(zhì)沉積和斑塊形成的作用。高脂飼養(yǎng)條件下芹菜素具有抑制血漿脂質(zhì)（TC、TG、LDL-C和HDL-C）水平升高的作用。生物信息學(xué)分析發(fā)現(xiàn)動(dòng)脈粥樣硬化時(shí)病變血管FBP1表達(dá)升高。分子對(duì)接發(fā)現(xiàn)FBP1與芹菜素之間存在較好的結(jié)合活性。芹菜素具有抑制病變血管FBP1表達(dá)的作用。結(jié)論 芹菜素抑制動(dòng)脈粥樣硬化作用機(jī)制與調(diào)控FBP1表達(dá)有關(guān)。

Objective This study aims to investigate the role of apigenin in regulating atherosclerosis and its potential targets. Methods A total of 32 ApoE^-/- mice were randomly divided into four groups: control group, model group, apigenin low- and high- doses (10 30 mg·kg^-1) group. An atherosclerosis model was established by feeding a high-cholesterol diet. After 70 d of feeding, the blood vessels (from the aortic root to the thoracic aorta) of the experimental animals were isolated for Oil Red O staining. Hematoxylin and eosin (HE) staining was used to detect vascular and aortic valve plaques. Enzyme-linked immunosorbent assay (ELISA) was performed to measure serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Network pharmacology methods were used to screen the targets of apigenin, and differential analysis was conducted in conjunction with gene expression data to identify key genes. Single-cell transcriptomics analysis was performed to assess the expression of key genes in different cell types. Results Compared to the high-fat group, apigenin treatment inhibited lipid deposition in the vascular wall and plaque formation. Under high-fat feeding conditions, apigenin suppressed the increase in plasma lipid levels (CHO, TG, LDL-C, and HDL-C). Bioinformatics analysis revealed that the expression of FBP1 was elevated in the diseased vessels during atherosclerosis. Molecular docking indicated a good binding affinity between FBP1 and apigenin. Apigenin treatment was found to inhibit the expression of FBP1 in diseased vessels. Conclusion The inhibition of atherosclerosis by apigenin is associated with the regulation of FBP1 expression.

R285.5

黑龍江省省屬本科高?！皟?yōu)秀青年教師基礎(chǔ)研究支持計(jì)劃”（YQJH2023035）；海燕科研基金面上項(xiàng)目（JJMS2022-16）