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Title:: Effects of losartan on pathogenesis of atherosclerosis in ApoE genedeficient mice

作者:: 何继强¹; 刘晓惠¹; 王绿娅²; 秦彦文²; 方薇³; 王伟³; 首都医科大学附属北京安贞医院： 1.心内科, 3.病理科；2.北京市心肺血管疾病研究所动脉粥样硬化研究室, 北京 100029

Author(s):: HE Ji-qiang¹; LIU Xiao-hui¹; WANG Lu-ya²; QAN Yan-wen²; FANG Wei³; WANG Wei³; 1.Department of Cardiology, Beijing Anzhen Hospital； 2.Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China

关键词:: 氯沙坦; 小鼠; 载脂蛋白E基因缺陷; 动脉粥样硬化; 抗氧化

Keywords:: losartan; mice; apoE genedeficient; atherosclerosis; antioxidation

分类号:: R541.4;R972.6

DOI:: -

文献标识码:: A

摘要:: 目的观察血管紧张素II 1型受体拮抗剂氯沙坦对载脂蛋白E基因缺陷小鼠主动脉粥样硬化病变形成的影响。方法 27只雄性载脂蛋白E基因缺陷小鼠随机分成3组，每组9只：对照组、氯沙坦低剂量组［5 mg/(kg·d)］及氯沙坦高剂量组［25 mg/(kg·d)］，灌胃，1次/d，0.3 ml，16周后处死动物。酶法测定血脂水平，比色法测定血清一氧化氮含量、超氧化物歧化酶活力和丙二醛水平；透射电镜观察主动脉病理形态学结构；采用HE染色法，计算机图像扫描、定量分析主动脉斑块大小及斑块占管腔面积之比。结果 3组间血脂水平无显著性差异；与对照组比较，氯沙坦低、高剂量组血清一氧化氮水平和超氧化物歧化酶活力均显著升高（P<0.01）、丙二醛水平显著减低（P<0.05和P<0.01），且两治疗组间也有显著差异（P<0.01）；氯沙坦干预后主动脉内皮损伤明显轻于对照组；氯沙坦组主动脉斑块面积及斑块面积与管腔面积之比值均显著低于对照组（P<0.01），且高剂量组较低剂量组作用更显著（P<0.01）。结论氯沙坦可通过增强载脂蛋白E基因缺陷小鼠抗氧化能力减轻主动脉粥样硬化的程度，且高剂量较低剂量作用更明显，而与其调节血脂代谢作用无关。

Abstract:: AIM To investigate the effects of losartan on the pathogenesis of atherosclerosis (AS) in ApoE genedeficient (ApoE-/-) mice. METHODS Twenty seven male ApoE -/-mice were randomly divided into three groups: control group (n=9), losartan lowdose group 5 mg/(kg·d) and losartan highdose group 25 mg/(kg·d). After 16 weeks of therapy with drugs by gastric gavage (once a day, 0.3 ml), the mice were killed. The levels of serum lipid and nitric oxide （NO）, superoxide dismutase (SOD) and malondialdehyde （MDA）were measured and aortic paraffin slices were prepared for histomorphological observation. The atherosclerotic plaque area and the ratio of plaque area to lumen area were determined by histochemical method. RESULTS There were no significant differences in serum lipid between treatment groups and control group. Compared with those of control group, the serum NO and SOD levels of losartan groups were significantly increased (P<0.01), the content of MAD was markedly decreased（P<0.05 and P<0.01, respectively）, with significant differences in NO, SOD and MAD levels between treatment groups（P<0.01）. The endothelial damage of the aortas in losartan groups was less severe than that of control group. The plaque areas （PA） and the ratio of plaque areas to lumen areas（PA/LA） of losartan groups were significantly lower than those of control group (P<0.01), and the PA and PA/LA were also significantly different between treatment groups（P<0.01）. CONCLUSION Losartan to some extent attenuates the development of AS in ApoE-/-mice by enhancing the antioxidation capacity. The effect of highdose losartan group is stronger than that of lowdose group but the influence is probably independent of lipidregulation.

参考文献/References

［1］何继强, 王绿娅, 刘晓惠. 血管紧张素II与动脉粥样硬化形成的研究进展［J］. 中国动脉硬化杂志, 2004, 12(3): 360-362.

［2］ Gross CM, Gerbaulet S, Quensel C, et al. Angiotensin II type 1 receptor expression in human coronary arteries with variable degrees of atherosclerosis［J］. Basic Res Cardiol, 2002, 97(4): 327-333.

［3］ Rueckschloss U, Quinn MT, Holtz J, et al. Dosedependent regulation of NAD(P)H oxidase expression by angiotensin II in human endothelial cells： protective effect of angiotensin II type 1 receptor blockade in patients with coronary artery disease［J］. Arterioscler Thromb Vasc Biol, 2002, 22(11): 1845-1851.

［4］ Cathcart MK. Regulation of superoxide anion production by NAD(P)H oxidase in monocytes/macrophages: contributions to atherosclerosis［J］. Arterioscler Thromb Vasc Biol, 2004, 24(1): 23-28.

［5］林燕, 黄维义, 李著华. 氧化应激致动脉粥样硬化作用的研究进展［J］. 黑龙江医学, 2004, 28(7): 517-519.

［6］ Ross R. Atherosclerosis——an inflammatory disease［J］. N Engl J Med，1999,340(2):115-126.

［7］ Yamaguchi Y, Kunitomo M, Haginaka J. Assay methods of modified lipoproteins in plasma［J］ . J Chromatogr B Analyt Technol Biomed Life Sci, 2002, 781(1-2): 313-330.

［8］ Hornig B, Landmesser U, Kohler C, et al. Comparative effect of ace inhibition and angiotensin II type 1 receptor antagonism on bioavailability of Nitric Oxide in patients with coronary artery disease: Role of superoxide dismutase［J］. Circulation, 2001, 103(6): 799-805.

［9］ Ferrario CM. Use of angiotensin II receptor blockers in animal models of atherosclerosis［J］. Am J Hypertens, 2002, 15(1 pt 2): 9s-13s.

［10］Fennessy PA, Campbell JH, Mendelsohn FA, et al. Angiotensinconverting enzyme inhibitors and atherosclerosis: relevance of animal models to human disease［J］. Clin Exp Pharmacol Physiol, 1996, 23(8):S30-S32.

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氯沙坦对载脂蛋白E基因缺陷小鼠动脉粥样硬化的影响(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

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