Li Wei, Hellsten Anna, Jacobsson Leif S, Blomqvist Henrik M, Olsson Anders G, Yuan Xi-Ming
Division of Pathology-II, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
J Mol Cell Cardiol. 2004 Nov;37(5):969-78. doi: 10.1016/j.yjmcc.2004.07.009.
The composition of atherosclerotic plaques, not just macroscopical lesion size, has been implicated in their susceptibility to rupture and the risk of thrombus formation. By focusing on the quality of lipids, macrophages, apoptosis, collagen, metalloproteinase expression and plaque integrity, we evaluated the possible anti-atherosclerotic effect of the antioxidants alpha-tocopherol and astaxanthin in Watanabe heritable hyperlipidemic (WHHL) rabbits. Thirty-one WHHL rabbits were divided into three groups and were fed a standard diet, as controls (N =10), or a standard diet with the addition of 500 mg alpha-tocopherol per kg feed (N =11) or 100 mg astaxanthin per kg feed (N =10) for 24 weeks. We found that both antioxidants, particularly astaxanthin, significantly decreased macrophage infiltration in the plaques although they did not affect lipid accumulation. All lesions in the astaxanthin-treated rabbits were classified as early plaques according to the distribution of collagen and smooth muscle cells. Both antioxidants also improved plaque stability and significantly diminished apoptosis, which mainly occurred in macrophages, matrix metalloproteinase three expressions and plaque ruptures. Although neither antioxidant altered the positive correlations between the lesion size and lipid accumulation, the lesion size and apoptosis were only positively correlated in the control group. Astaxanthin and alpha-tocopherol may improve plaque stability by decreasing macrophage infiltration and apoptosis in this atherosclerotic setting. Apoptosis reduction by alpha-tocopherol and astaxanthin may be a new anti-atherogenic property of these antioxidants.
动脉粥样硬化斑块的组成，而非仅仅宏观病变大小，与其破裂易感性及血栓形成风险有关。通过关注脂质、巨噬细胞、细胞凋亡、胶原蛋白、金属蛋白酶表达及斑块完整性的质量，我们评估了抗氧化剂α-生育酚和虾青素对渡边遗传性高脂血症（WHHL）兔的潜在抗动脉粥样硬化作用。31只WHHL兔被分为三组，分别给予标准饮食作为对照（N = 10），或在标准饮食基础上每千克饲料添加500毫克α-生育酚（N = 11）或每千克饲料添加100毫克虾青素（N = 10），持续24周。我们发现，两种抗氧化剂，尤其是虾青素，显著减少了斑块中的巨噬细胞浸润，尽管它们并未影响脂质积累。根据胶原蛋白和平滑肌细胞的分布，虾青素处理组兔子的所有病变均被归类为早期斑块。两种抗氧化剂还改善了斑块稳定性，并显著减少了细胞凋亡，细胞凋亡主要发生在巨噬细胞中，同时还减少了基质金属蛋白酶3的表达和斑块破裂。尽管两种抗氧化剂均未改变病变大小与脂质积累之间的正相关关系，但病变大小与细胞凋亡仅在对照组中呈正相关。在这种动脉粥样硬化环境中，虾青素和α-生育酚可能通过减少巨噬细胞浸润和细胞凋亡来改善斑块稳定性。α-生育酚和虾青素减少细胞凋亡可能是这些抗氧化剂的一种新的抗动脉粥样硬化特性。
