目的 研究商陆皂苷甲（EsA）对动脉粥样硬化（AS）大鼠的作用及机制。方法 将SD雄性大鼠随机分为对照组、模型组、辛伐他汀片（SIMT，10mg·kg^-1，阳性对照）组和EsA高、低剂量（10、2.5mg·kg^-1）组，每组6只。对照组给予普通饲料，其余各组以高脂饲料联合ip7×10⁵U·kg^-1维生素D₃（在第3天注射）制备AS模型。造模的同时ip给药，每天1次。采用全自动生化分析仪检测各组大鼠血清总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）水平；ELISA法检测血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）水平；HE染色法观察胸主动脉病理变化；Western blotting法检测胸主动脉Toll样受体4（TLR4）和髓样分化因子88（MyD88）蛋白表达；免疫组化法检测胸主动脉核因子κB（NF-κB） p65阳性细胞表达。结果 与对照组比较，模型组大鼠血清中TC、TG、LDL-C、TNF-α、IL-6和IL-1β水平显著升高（P＜0.01），HDL-C水平显著降低（P＜0.01）；胸主动脉血管内皮损伤严重，可见明显蓝色钙状斑块；胸主动脉TLR4和MyD88蛋白表达以及NF-κB p65阳性细胞表达显著升高（P＜0.01）。与模型组比较，EsA高、低剂量组大鼠血清血脂和炎性因子水平明显改善（P＜0.05、0.01）；胸主动脉血管内皮大致恢复正常，蓝色钙状斑块减少；胸主动脉TLR4和MyD88蛋白表达以及NF-κB p65阳性细胞表达显著降低（P＜0.05、0.01）。结论 EsA可能通过抑制TLR4/NF-κB信号通路对大鼠AS发挥改善作用。

Objective To investigate the effect and mechanism of esculentoside A (EsA) on rats with atherosclerosis (AS).Methods SD male rat were randomly divided into control group, model group, simvastatin (SIMT, positive drug, 10 mg·kg^-1) group, EsA high and low dose (10 and 2.5 mg·kg^-1) groups, with six rats in each group. The control group was given ordinary diet, and the other groups were given high fat diet combined with ip 7×10⁵ U·kg^-1 vitamin D₃ (injected on the third day) to prepare AS model, while administering once a day. After rat serum collection, automatic biochemical analyzer was used to detect serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) levels of rats in each group. Enzyme-linked immunoassay was used to detect serum cytokines Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), and Interleukin-1β (IL-1β) levels. HE staining method was used to analyze the pathological changes of thoracic aorta. Western blotting was used to detect the protein expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). Immunohistochemical staining was used to detect the expression of nuclear factor κB (NF-κB) p65 positive cells.Results Compared with the control group, the serum levels of TC, TG, LDL-C, TNF-α, IL-6, and IL-1β in the model group were significantly increased (P <0.01), and HDL-C was significantly decreased (P <0.01). The thoracic aorta vascular endothelium of rats in the model group was severely injured, which accompanied with obvious blue calcium-like plaques. The expression of TLR4 and MyD88 proteins and NF-κB p65 positive cells in thoracic aorta were significantly increased (P <0.01). Compared with model group, the levels of serum lipids and inflammatory factors in rats in the EsA groups were significantly improved (P <0.05 and 0.01). The endothelium of the thoracic aorta returned to normal and the blue calcium plaques decreased. The expression of TLR4 and MyD88 proteins and NF-κB p65 positive cells in thoracic aorta were significantly decreased (P <0.05 and 0.01).Conclusion EsA might play a therapeutic effect on AS rats by inhibiting TLR4/NF-κB signaling pathway.

R285.5

恩施州科学技术局指导性项目(2018年度)