Division of Cardiology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Atherosclerosis. 2011 Aug;217(2):350-7. doi: 10.1016/j.atherosclerosis.2011.03.042. Epub 2011 Apr 8.
We sought to examine the effect of resveratrol (3,4',5-trihydroxy-trans-stilbene), a plant-derived polyphenolic compound, on the development of abdominal aortic aneurysm (AAA).
AAA was induced in mice by periaortic application of CaCl(2). NaCl (0.9%)-applied mice were used as a sham group. Mice were treated with intraperitoneal injection of PBS (Sham/CON, AAA/CON, n=30 for each) or resveratrol (100 mg/kg/day) (AAA/RSVT, n=30). Six weeks after the operation, aortic tissue was excised for further examinations.
Aortic diameter was enlarged in AAA/CON compared with Sham/CON. Resveratrol treatment reduced the aneurysm size and inflammatory cell infiltration in the aortic wall compared with AAA/CON. Elastica Van Gieson staining showed destruction of the wavy morphology of the elastic lamellae in AAA/CON, while it was preserved in AAA/RSVT. The increased mRNA expression of monocyte chemotactic protein-1, tumor necrosis factor-α, intercellular adhesion molecule-1, CD68, vascular endothelial growth factor-A, p47, glutathione peroxidase (GPX)1 and GPX3 were attenuated by resveratrol treatment (all p<0.05). Administration of resveratrol decreased protein expression of phospho-p65 in AAA. The increased 8-hydroxy-2'-deoxyguanosine-positive cell count and 4-hydroxy-2-nonenal-positive cell count in AAA were also reduced by resveratrol treatment. Zymographic activity of matrix metalloproteinase (MMP)-9 and MMP-2 was lower in AAA/RSVT compared with AAA/CON (both p<0.05). Compared with AAA/CON, Mac-2(+) macrophages and CD31(+) vessels in the aortic wall were decreased in AAA/RSVT (both p<0.05).
Treatment with resveratrol in mice prevented the development of CaCl(2)-induced AAA, in association with reduced inflammation, oxidative stress, neoangiogenesis, and extracellular matrix disruption. These findings suggest therapeutic potential of resveratrol for AAA.
我们研究了白藜芦醇（3,4',5-三羟基反式二苯乙烯），一种植物来源的多酚化合物，对腹主动脉瘤（AAA）发展的影响。
通过在主动脉周围应用氯化钙诱导小鼠发生 AAA。用生理盐水（0.9%）处理的小鼠作为假手术组。用腹腔内注射磷酸盐缓冲液（假手术/对照，AAA/对照，每组 30 只）或白藜芦醇（100mg/kg/天）（AAA/RSVT，每组 30 只）处理小鼠。手术后 6 周，取出主动脉组织进行进一步检查。
与假手术/对照相比，AAA/对照的主动脉直径增大。与 AAA/对照相比，白藜芦醇治疗减少了腹主动脉瘤的大小和主动脉壁的炎症细胞浸润。弹力纤维 Van Gieson 染色显示 AAA/对照中弹性小动脉的波浪状形态破坏，而 AAA/RSVT 中则得到保留。白藜芦醇治疗可减弱单核细胞趋化蛋白-1、肿瘤坏死因子-α、细胞间黏附分子-1、CD68、血管内皮生长因子-A、p47、谷胱甘肽过氧化物酶（GPX）1 和 GPX3 的 mRNA 表达增加（均 p<0.05）。白藜芦醇治疗降低了 AAA 中磷酸化 p65 的蛋白表达。白藜芦醇治疗还降低了 AAA 中 8-羟基-2'-脱氧鸟苷阳性细胞计数和 4-羟基-2-壬烯醛阳性细胞计数的增加。与 AAA/对照相比，AAA/RSVT 中的基质金属蛋白酶（MMP）-9 和 MMP-2 的酶谱活性较低（均 p<0.05）。与 AAA/对照相比，AAA/RSVT 中主动脉壁的 Mac-2（+）巨噬细胞和 CD31（+）血管减少（均 p<0.05）。
在小鼠中用白藜芦醇治疗可预防氯化钙诱导的 AAA 的发生，同时减少炎症、氧化应激、新生血管形成和细胞外基质破坏。这些发现表明白藜芦醇对 AAA 具有治疗潜力。
