中文摘要：

目的观察大蒜素对高胆固醇饮食诱导的apoE^-/-小鼠动脉粥样硬化进展的影响,并从蛋白亚硝基化方面探讨其可能的作用机制。方法 30只apoE^-/-小鼠随机分3组：对照组（生理盐水,ig）、低剂量组（大蒜素,9mg/kg·d,ig）、高剂量组（大蒜素,18mg/kg·d,ig）。高胆固醇饮食喂养12周,分别于第0、4、8、12周采血检测血脂水平,处理结束后,检测血浆氧化低密度脂蛋白（ox-LDL）、丙二醛（MDA）、肿瘤坏死因子-α（TNF-α）和一氧化氮（NO）水平;利用苏木精伊红染色与范吉尔森弹性纤维染色观察主动脉根部组织学变化;免疫组化染色检测动脉粥样硬化斑块内巨噬细胞和血管平滑肌细胞含量;免疫荧光观察主动脉根部蛋白亚硝基化水平的变化。另外,以人脐静脉内皮细胞为体外模型,将其与ox-LDL（50μg/mL）共同培养24h,并用不同剂量（10μmol/L和20μmol/L）大蒜素加以处理,分别采用硝酸还原酶法和免疫荧光法检测细胞上清NO及细胞蛋白亚硝基化水平。结果组织学分析发现,大蒜素组小鼠主动脉根部斑块面积及斑块内巨噬细胞和血管平滑肌细胞含量明显较对照组少（P〈0.05）。与对照组相比,大蒜素组小鼠血浆MDA、ox-LDL、TNF-α水平明显降低（P〈0.05）,血浆NO水平及主动脉根部蛋白亚硝基化水平明显升高（P〈0.05）,但对其血脂水平无明显影响。体外实验结果显示,与对照组相比,大蒜素能够显著恢复由ox-LDL所导致的人脐静脉内皮细胞的NO和蛋白亚硝基化水平的减少（P〈0.01）。结论大蒜素能够有效抑制动脉粥样硬化的进展,其作用机制可能与大蒜素通过上调内皮细胞蛋白亚硝基化水平所发挥抗氧化应激和抗炎作用有关。

英文摘要：

Objective To investigate the effect of allicin on the development of atherosclerosis in apoE^-/- mice and explore its underlying mechanism from the perspective of protein S-nitrosylation.Methods Thirty male apoE^-/- mice were randomly divided into 3 groups：control group （saline,ig）,low-dose group （allicin,9 mg/kg·d, ig）and high-dose group （allicin,18 mg/kg·d,ig）.They were fed with high cholesterol diet for 12 weeks.The levels of plasma lipids,oxidized-LDL （ox-LDL）,malondialdehyde,tumor necrosis factor-alpha and nitric oxide （NO）were measured.The atherosclerotic lesions in aortic root were evaluated after hematoxylin and eosin staining and elastica van Gieson and immunohistochemical staining,respectively.Furthermore,in vitro experiments were performed using human umbilical vein endothelial cells （HUVECs）.The HUVECs were treated with allicin （10μmol/L or 20 μmol/L）for 24 hours in the presence of ox-LDL （50 μg/mL）.The level of NO in supernatant was measured by a nitrate/nitrite assay. The protein S-nitrosylation of the HUVECs was detected through immunofluorescence.Results The histological analysis revealed that allicin treatment not only significantly decreased the areas of the atherosclerotic lesion （all P 〈0.05）but also suppressed the macrophage accumulation and smooth muscle cell proliferation in the lesion.There was no significant difference in the levels of plasma lipids between control and treated groups.However,allicin exerted obvious anti-oxidative and anti-inflammatory effects. Interestingly,the allicin treatment led to marked increase of the plasma NO level （P 〈0.05）and aortic protein S-nitrosylation.The experiments in vitro further proved that the allicin up-regulated the levels of NO and protein S-nitrosylation in HUVECs treated with ox-LDL （P 〈 0.01 ）.Conclusion Allicin can inhibit the development of atherosclerosis.The mechanism is associated with the up-regulation of protein S-nitrosylation in endothelial cells, which plays an important role in