Glycosylated HDL affects the stability of carotid atherosclerotic plaque in ApoE-/- mice
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摘要: 目的:探究糖基化高密度脂蛋白 (HDL) 对载脂蛋白E (ApoE) -/-小鼠颈动脉粥样斑块稳定性的影响。方法:通过ApoE-/-小鼠颈动脉套管手术配合高脂饮食的方式诱导小鼠动脉粥样硬化斑块的模型, 将术后4周经后尾静脉注射糖基化HDL的ApoE-/-小鼠设为G-HDL组, 注射正常HDL的小鼠设为HDL组, 注射磷酸盐缓冲液 (PBS) 的小鼠设为PBS组;术后6周将小鼠安乐处死, 取小鼠的颈动脉进行组织病理和免疫组织化学检查。结果:3组间血脂水平和体质量差异无统计学意义 (P ≥ 0.05)。与HDL组相比, 苏木精-伊红染色显示GHDL组颈动脉斑块体积较小、粥样斑块内纤维帽细薄、脂质核心大融合成片, 管腔狭窄程度较轻;油红O染色颈动脉斑块内红染区域明显增多 (P<0.05);Masson染色显示斑块内胶原面积显著减少 (P<0.05);免疫组织化学检测显示平滑细胞和巨噬细胞增多。结论:G-HDL不影响血脂水平, 通过增加斑块内脂质沉积、斑块内纤维帽变薄和巨噬细胞增加, 使得动脉粥样斑块不稳定, 本研究为糖尿病动脉粥样硬化的防治提供新的方向。Abstract: Objective: To Investigate the effects of glycosylated HDL on the stability of carotid atherosclerotic plaques in ApoE-/-mice.Method: The atherosclerotic plaque model of mice was induced by carotid cannulation of ApoE-/-mice combined with a high-fat diet.Glycosylated HDL was injected into the ApoE-/-mice by tail vein after 4 weeks of surgery.The control group received normal HDL injection and the blank control group received PBS.Mice were sacrificed safely after 6 weeks of surgery.Mouse carotid artery was taken for pathologic and immunohistochemical staining.Result: There was no significant difference of blood lipid levels and body weight among the three groups (P>0.05).Compared with control group, Glycosylated HDL group showed smaller plaque volume, more thin fibrous cap in the atherosclerotic plaque, and larger fused lipid core.Additionally, in the glycosylated HDL group, the lumen was narrower, and oil red O staining showed that the area of red staining was significantly bigger when compared with control group (P<0.05).Lastly, the area of collagen in the plaque was significantly reduced, and the number of smooth cell and macrophage was significantly increased in the glycosylated HDL group (all P<0.05).Conclusion: G-HDL affects the stability of atherosclerotic plaque by increasing lipid deposition in the plaque, reducing thickness of the fibrous caps and increasing the number of macrophages without affecting blood lipid levels.The finding offers a new direction for prevention and treatment of diabetes-atherosclerosis.
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Key words:
- glycosylated HDL /
- atherosclerosis /
- stability
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