摘要
目的探讨在兔动脉粥样硬化斑块模型中过氧化物酶体增殖物激活受体(PPAR)-γ的表达水平及其作用。方法将新西兰雄性大白兔随机分入正常饮食组、高脂饮食组(6周、10周)、高脂饮食+血管拉伤手术组(6周、10周)。采用高脂饮食和动脉内膜球囊损伤的方法建立动脉粥样硬化斑块的模型。通过苏木精-伊红染色观察动脉粥样硬化斑块的病理学变化,采用免疫组织化学法、Western印迹法和实时反转录聚合酶链反应检测兔血管组织PPAR-γ蛋白和mRNA表达水平,酶联免疫吸附试验检测实验第4、6、8、10周的血清肿瘤坏死因子(TNF)-α、P选择素和基质金属蛋白酶(MMP)-9水平。结果高脂饮食6周组与正常饮食组血管组织中PPAR-γ蛋白和mRNA表达量的差异均无统计学意义(P值均>0.05)。高脂饮食10周组、高脂饮食J6周+血管拉伤组和高脂饮食10周+血管拉伤组的PPAR-γ蛋白和mRNA表达量均显著高于正常饮食组(P值均<0.01),且高脂饮食10周+血管拉伤组均显著高于高脂饮食10周组(P值均<0.01)。高脂饮食10周组和高脂饮食10周+血管拉伤组在实验第4、6、8、10周时的TNF-α、P选择素和MMP-9水平均显著高于正常饮食组同时间(P值均<0.01),高脂饮食10周组在实验第8、10周时的上述指标水平均显著低于高脂饮食10周+血管损伤组同时间(P值均<0.05)。结论 PPAR-γ在动脉粥样硬化斑块病变严重处表达增强,通过调控炎性反应,起到促进动脉粥样硬化病变的作用。
Objective To investigate the effect of peroxisome proliferator-activated receptor (PPAR)-y on atherosclerosis in rabbits. Methods Male New Zealand rabbits were randomly divided into 5 groups: normal diet group, high-fat diet groups (6 weeks and 10 weeks), and high-fat diet+ balloon-injury groups (6 weeks and 10 weeks). Atherosclerosis was induced by high-fat diet and balloon angioplasty. Tissue structures in artery samples were observed bY hematoxylin and eosin staining. Immunohistochemistry and Western blot analysis were used to detect the expression of PPAR-y protein and the expression of PPAR-y mRNA was determined by real-time quantitative PCR. Tumor necrosis factor (TNF)-a, P-selectin and matrix metalloproteinase (MMP)-9 were measured at the 4th week, 6th week, 8th week, 10th week of the experiment. Results There were no significant differences in the expression of PPAR-y protein or mRNA between 6-week high-fat diet group and normal diet group (all P〉0.05). In the 10-week high-fat diet. group and high-fat diet-t-balloon-injury groups, the expression of PPAR-y protein and mRNA were significantly increased as compared with the normal diet group (all P〈0.01). The expression of PPAR-y protein and mRNA in the 10-week high-fat diet+ balloon-injury group were significantly higher than that in the 10-week high-fat diet group (both P〈0.01 ). The levels of TNF-a , P-selectin and MMP-9 in the 10-week high-fat diet group and 10-week high-fat diet+ balloon-injury group were all significantly higher than those in the normal diet group (all P〈0.01 ). The above-mentioned parameters at the 8th week and 10th week of the experiment in the 10-week high-fat diet group were significantly lower than those in the 10-week high-fat diet+ balloon-injury group (all P 〈 0.05). Conclusion The expression of PPAR-y is increased in severe atherosclerotic plaque, indicating that PPAR-y play a role in the development of atherosclerosis by regulating inflammatory response.
出处
《上海医学》
CAS
CSCD
北大核心
2014年第3期223-226,I0002,共5页
Shanghai Medical Journal
基金
国家自然科学基金资助项目(30791265)