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瑞舒伐他汀对载脂蛋白E基因敲除小鼠动脉粥样硬化模型心血管形态和功能的影响。

Effects of rosuvastatin on cardiovascular morphology and function in an ApoE-knockout mouse model of atherosclerosis.

作者信息

Grönros J, Wikström J, Brandt-Eliasson U, Forsberg G B, Behrendt M, Hansson G I, Gan L M

机构信息

Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.

出版信息

Am J Physiol Heart Circ Physiol. 2008 Nov;295(5):H2046-53. doi: 10.1152/ajpheart.00133.2008. Epub 2008 Sep 12.

Abstract

This study investigated the effects of rosuvastatin on plaque progression and in vivo coronary artery function in apolipoprotein E-knockout (ApoE-KO) mice, using noninvasive high-resolution ultrasound techniques. Eight-week-old male ApoE-KO mice (n = 20) were fed a high-fat diet with or without rosuvastatin (10 micromol.kg(-1).day(-1)) for 16 wk. When compared with control, rosuvastatin reduced total cholesterol levels (P < 0.05) and caused significant retardation of lesion progression in the brachiocephalic artery, as visualized in vivo using an ultrasound biomicroscope (P < 0.05). Histological analysis confirmed the reduction of brachiocephalic atherosclerosis and also revealed an increase in collagen content in the statin-treated group (P < 0.05). Coronary volumetric flow was measured by simultaneous recording of Doppler velocity signals and left coronary artery morphology before and during adenosine infusion. The hyperemic flow in response to adenosine was significantly greater in left coronary artery following 16 wk of rosuvastatin treatment (P < 0.001), whereas the baseline flow was similar in both groups. In conclusion, rosuvastatin reduced brachiocephalic artery atherosclerotic plaques in ApoE-KO mice. Coronary artery function assessed using recently developed in vivo ultrasound-based protocols, also improved.

摘要

本研究采用非侵入性高分辨率超声技术,调查了瑞舒伐他汀对载脂蛋白E基因敲除(ApoE-KO)小鼠斑块进展及体内冠状动脉功能的影响。8周龄雄性ApoE-KO小鼠(n = 20)被给予含或不含瑞舒伐他汀(10微摩尔·千克⁻¹·天⁻¹)的高脂饮食,持续16周。与对照组相比,瑞舒伐他汀降低了总胆固醇水平(P < 0.05),并使头臂动脉病变进展显著延缓,这在使用超声生物显微镜进行体内观察时可见(P < 0.05)。组织学分析证实头臂动脉粥样硬化减轻,且还显示他汀治疗组的胶原蛋白含量增加(P < 0.05)。通过在腺苷输注前后同时记录多普勒速度信号和左冠状动脉形态来测量冠状动脉容积流量。瑞舒伐他汀治疗16周后,左冠状动脉对腺苷的充血性血流显著增加(P < 0.001),而两组的基线血流相似。总之,瑞舒伐他汀减少了ApoE-KO小鼠的头臂动脉粥样硬化斑块。使用最近开发的基于体内超声的方案评估的冠状动脉功能也得到了改善。

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