Jiang F, Jones G T, Dusting G J
Bernard O'Brien Institute of Microsurgery, The University of Melbourne, Fitzroy, Victoria, Australia.
Br J Pharmacol. 2007 Nov;152(6):880-90. doi: 10.1038/sj.bjp.0707449. Epub 2007 Sep 10.
Oxidative stress may be involved in the development of abdominal aortic aneurysms (AAAs). Previous studies indicate that antioxidants protect against AAA formation during chronic angiotensin (Ang) II infusion in apolipoprotein E-deficient (ApoE(0)) mice. We here examine if these protective effects also occurred in aged ApoE(0) mice.
Male ApoE(0) mice (50-60 weeks) were randomly divided into 4 groups: saline, Ang II (1000 ng kg(-1) min(-1) for 4 weeks), Ang II plus antioxidants (0.1% vitamin E in food plus 0.1% vitamin C in drinking water), and Ang II plus losartan (30 mg kg(-1) day(-1)).
Exogenous Ang II increased systolic blood pressure by 40 mmHg and resulted in the formation of pseudoaneurysms (rupture and extramural haematoma) in the abdominal aorta in 50% of animals. True aneurysmal dilatation was rarely observed. Antioxidants decreased systemic oxidative stress (plasma malondialdehyde), but had only minor effects on aortic rupture, relative to the complete prevention by losartan. Immunohistochemistry revealed strong matrix metalloproteinase-9 (MMP-9) expression in atherosclerotic plaques and at the sites of rupture. Antioxidants did not affect tumour necrosis factor-alpha-stimulated MMP-9 release from U937 cells. In addition, antioxidants had little effects on Ang II-induced renal dysfunction.
In contrast to previous findings in younger mice, antioxidants had only minor effects on Ang II-induced aortic rupture in aged mice. Our results demonstrate that the pathological features of the aneurysmal remodelling induced by Ang II in old ApoE(0) mice are distinct from those of human AAA.
氧化应激可能参与腹主动脉瘤（AAA）的发生发展。先前的研究表明，抗氧化剂可在载脂蛋白E缺陷（ApoE(0)）小鼠慢性输注血管紧张素（Ang）II期间预防AAA形成。我们在此研究这些保护作用在老年ApoE(0)小鼠中是否也会出现。
将雄性ApoE(0)小鼠（50 - 60周龄）随机分为4组：生理盐水组、Ang II组（1000 ng·kg⁻¹·min⁻¹，持续4周）、Ang II加抗氧化剂组（食物中含0.1%维生素E，饮用水中含0.1%维生素C）以及Ang II加氯沙坦组（30 mg·kg⁻¹·天⁻¹）。
外源性Ang II使收缩压升高40 mmHg，并导致50%的动物腹主动脉形成假性动脉瘤（破裂和壁外血肿）。很少观察到真性动脉瘤扩张。相对于氯沙坦的完全预防作用，抗氧化剂降低了全身氧化应激（血浆丙二醛），但对主动脉破裂仅有轻微影响。免疫组织化学显示，基质金属蛋白酶-9（MMP-9）在动脉粥样硬化斑块和破裂部位有强烈表达。抗氧化剂不影响肿瘤坏死因子-α刺激的U937细胞释放MMP-9。此外，抗氧化剂对Ang II诱导的肾功能障碍影响很小。
与先前在年轻小鼠中的发现相反，抗氧化剂对老年小鼠中Ang II诱导的主动脉破裂仅有轻微影响。我们的结果表明，老年ApoE(0)小鼠中Ang II诱导的动脉瘤重塑的病理特征与人类AAA不同。
