目的 研究商陸皂苷甲（EsA）對動脈粥樣硬化（AS）大鼠的作用及機制。方法 將SD雄性大鼠隨機分為對照組、模型組、辛伐他汀片（SIMT，10mg·kg^-1，陽性對照）組和EsA高、低劑量（10、2.5mg·kg^-1）組，每組6只。對照組給予普通飼料，其余各組以高脂飼料聯(lián)合ip7×10⁵U·kg^-1維生素D₃（在第3天注射）制備AS模型。造模的同時ip給藥，每天1次。采用全自動生化分析儀檢測各組大鼠血清總膽固醇（TC）、三酰甘油（TG）、低密度脂蛋白膽固醇（LDL-C）和高密度脂蛋白膽固醇（HDL-C）水平；ELISA法檢測血清腫瘤壞死因子-α（TNF-α）、白細胞介素-6（IL-6）和白細胞介素-1β（IL-1β）水平；HE染色法觀察胸主動脈病理變化；Western blotting法檢測胸主動脈Toll樣受體4（TLR4）和髓樣分化因子88（MyD88）蛋白表達；免疫組化法檢測胸主動脈核因子κB（NF-κB） p65陽性細胞表達。結(jié)果 與對照組比較，模型組大鼠血清中TC、TG、LDL-C、TNF-α、IL-6和IL-1β水平顯著升高（P＜0.01），HDL-C水平顯著降低（P＜0.01）；胸主動脈血管內(nèi)皮損傷嚴重，可見明顯藍色鈣狀斑塊；胸主動脈TLR4和MyD88蛋白表達以及NF-κB p65陽性細胞表達顯著升高（P＜0.01）。與模型組比較，EsA高、低劑量組大鼠血清血脂和炎性因子水平明顯改善（P＜0.05、0.01）；胸主動脈血管內(nèi)皮大致恢復(fù)正常，藍色鈣狀斑塊減少；胸主動脈TLR4和MyD88蛋白表達以及NF-κB p65陽性細胞表達顯著降低（P＜0.05、0.01）。結(jié)論 EsA可能通過抑制TLR4/NF-κB信號通路對大鼠AS發(fā)揮改善作用。

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

恩施州科學(xué)技術(shù)局指導(dǎo)性項目(2018年度)