目的 探讨芹菜素调控动脉粥样硬化的作用及其潜在作用靶点。方法 将32只ApoE^-/-小鼠随机分为对照组、模型组和芹菜素低、高剂量（10、30 mg·kg^-1）组，通过高胆固醇饲料喂养建立动脉粥样硬化模型。实验动物饲养70 d后，分离各组实验动物血管（主动脉根部至胸主动脉）并进行油红O染色，同时应用苏木精-伊红（HE）染色检测血管及主动脉瓣斑块。酶联免疫吸附（ELISA）法检测血清中总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白-胆固醇（HDL-C）和低密度脂蛋白-胆固醇（LDL-C）。使用网络药理学方法筛选芹菜素的靶点，并结合基因表达数据进行差异分析，确定关键基因。通过单细胞转录组学分析关键基因在不同细胞类型中的表达，并使用分子对接技术验证芹菜素与关键基因的结合活性。结果与模型组相比，芹菜素具有抑制血管壁脂质沉积和斑块形成的作用。高脂饲养条件下芹菜素具有抑制血浆脂质（TC、TG、LDL-C和HDL-C）水平升高的作用。生物信息学分析发现动脉粥样硬化时病变血管FBP1表达升高。分子对接发现FBP1与芹菜素之间存在较好的结合活性。芹菜素具有抑制病变血管FBP1表达的作用。结论 芹菜素抑制动脉粥样硬化作用机制与调控FBP1表达有关。

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

黑龙江省省属本科高校“优秀青年教师基础研究支持计划”（YQJH2023035）；海燕科研基金面上项目（JJMS2022-16）