Department of Cardiology, Shanghai First People's Hospital, College of Medicine, Shanghai Jiaotong University, Shanghai 200080, PR China.
Mol Med Rep. 2013 Mar;7(3):862-8. doi: 10.3892/mmr.2013.1282. Epub 2013 Jan 21.
Peroxisome proliferator-activated receptor α (PPAR-α) has been detected in the liver, kidney, heart and skeletal muscle. The expression and mechanism of PPAR-α in atherosclerosis remains unclear. The present study was undertaken in order to examine the expression and role of PPAR-α in programmed atherosclerosis induced by a high‑fat diet and balloon-injury in rabbits. Rabbits were randomly divided into 3 groups: control, high-fat diet and high-fat diet+balloon‑injury groups. The high-fat diet and high-fat diet+balloon-injury groups were further divided into 6-, 8- and 10-week groups. Real-time quantitative PCR analysis was used to detect PPAR-α mRNA and immunohistochemistry (IHC) and western blot analysis were used to examine PPAR-α protein expression. Tumor necrosis factor (TNF)-α, interleukin (IL)-10 and P-selectin levels in the rabbits were measured by enzyme-linked immunosorbent assay (ELISA). In the high-fat or high-fat diet+balloon-injury groups, the vascular thickness was markedly higher than in the control group (P<0.01). PPAR-α protein and mRNA were significantly increased in the high-fat diet group as compared with the control group (P<0.01). Furthermore, there were marked changes from 6 to 10 weeks in the high-fat diet group (P<0.01). Compared with the control group, PPAR-α protein and mRNA were increased in the high-fat diet+balloon-injury group (P<0.01). There were significant differences of PPAR-α protein and mRNA at various time points in the high-fat diet+balloon‑injury group, as shown by real-time quantitative PCR and IHC (P<0.01). As shown by western blotting, there were no differences between the high-fat diet + balloon-injury 8- and 10-week groups (P>0.05). In those arteries that were occluded by ≥60%, PPAR-α expression was lower than that in the arteries which were occluded <60% in the high‑fat diet+balloon-injury 10-week group. In the high-fat diet and high-fat diet+balloon-injury groups, the levels of IL-10, TNF-α and P-selectin were upregulated compared with the control group. However, from weeks 8 to 10, TNF-α and P-selectin were decreased and IL-10 was still increased in the high-fat diet+balloon-injury group. The results of this study demonstrate that PPAR-α has preventive effects on atherosclerosis, which may be related to the regulation of inflammation.
过氧化物酶体增殖物激活受体 α（PPAR-α）已在肝脏、肾脏、心脏和骨骼肌中被检测到。PPAR-α 在动脉粥样硬化中的表达和机制尚不清楚。本研究旨在研究高脂饮食和球囊损伤诱导的程序性动脉粥样硬化中 PPAR-α 的表达和作用。兔子被随机分为 3 组：对照组、高脂饮食组和高脂饮食+球囊损伤组。高脂饮食组和高脂饮食+球囊损伤组进一步分为 6、8 和 10 周组。实时定量 PCR 分析用于检测 PPAR-α mRNA，免疫组化（IHC）和 Western blot 分析用于检测 PPAR-α 蛋白表达。通过酶联免疫吸附试验（ELISA）测量兔子中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-10 和 P-选择素的水平。在高脂饮食或高脂饮食+球囊损伤组中，血管厚度明显高于对照组（P<0.01）。与对照组相比，高脂饮食组中 PPAR-α 蛋白和 mRNA 显著增加（P<0.01）。此外，高脂饮食组从 6 周到 10 周有明显变化（P<0.01）。与对照组相比，高脂饮食+球囊损伤组中 PPAR-α 蛋白和 mRNA 增加（P<0.01）。实时定量 PCR 和 IHC 显示，高脂饮食+球囊损伤组各时间点的 PPAR-α 蛋白和 mRNA 均有显著差异（P<0.01）。Western blot 显示，高脂饮食+球囊损伤 8 周和 10 周组之间无差异（P>0.05）。在高脂饮食+球囊损伤 10 周组中，闭塞程度≥60%的动脉中 PPAR-α 表达低于闭塞程度<60%的动脉。在高脂饮食组和高脂饮食+球囊损伤组中，IL-10、TNF-α 和 P-选择素的水平与对照组相比均升高。然而，从第 8 周到第 10 周，TNF-α 和 P-选择素下降，而 IL-10 仍在高脂饮食+球囊损伤组中升高。本研究结果表明，PPAR-α 对动脉粥样硬化具有预防作用，这可能与炎症的调节有关。
