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作 者:胡朝晖[1] 邹云增[1] 杨茗[1] 周涛[2] 葛均波[1]
机构地区:[1]复旦大学附属中山医院心内科上海市心血管病研究所,上海200032 [2]复旦大学附属中山医院血管外科,上海200032
出 处:《中国实验动物学报》2009年第1期15-20,I0004,共7页Acta Laboratorium Animalis Scientia Sinica
基 金:973子课题(编号:2007CB512003);上海市国际科技合作项目(编号:074107020);教育部博士点基金(编号:2006226)
摘 要:目的通过高脂喂养兔制造动脉粥样硬化动物模型,研究G-CSF对不同动脉段内皮形态和功能变化的影响及相互关系。方法30只新西兰成年雄兔随机分4组,分为对照组6只,高脂喂养组、普通及高脂喂养+G-CSF组各8只,分别测定血脂及血清NO浓度,各取胸主动脉、颈总动脉、股动脉,采用病理分析及扫描电镜观察内皮形态的不同变化,同时用RT-PCR方法测定eNOS、ET-1基因的表达了解不同动脉段的内皮功能变化。结果高脂喂养后兔血脂、NO浓度明显升高,病理发现动脉内膜增厚,以大动脉最著,小动脉最次,扫描电镜下内皮细胞的凋亡、变形亦然。ET-1基因表达相对定量次序为胸主动脉>颈总动脉>股动脉,eNOS基因反之。应用G-CSF后大动脉内皮功能及形态受到明显影响,但小型动脉变化不大。结论高脂喂养兔能成功制造动脉粥样硬化模型,成模后动脉内皮功能显著受损,其中以大型动脉显著,同时内皮形态出现相应变化。应用G-CSF对全身动脉系统有影响,且动脉越小,影响越小,说明粥样硬化动脉内皮形态与功能改变之间存在必然联系,对G-CSF的反应也不同。Objective To study the changes of endothelial morphology and function after G-CSF injection,the relation between the changes and their location at different artery segments in rabbit models of atherosclerosis,fed by high_fat diet.Methods 30 New Zealand male white rabbits were divided into 4 groups randomly.The blood lipid level and NO concentration were measured.Thoracic aorta,carotid artery and femoral artery were taken for light and scanning electron microscopic examination to assess the morphological changes of endothelial cells.Endothelial function was examined by RT-PCR to test the expression of eNOS and ET-1 gene in different sites.Results The lipid level and NO concentration were higher in the animals of atherosclerosis model group.Pathological observation revealed that the arterial intima thickening in this group and the process were more serious in larger artery.Meanwhile,apoptosis and distortion of endothelial cells discovered by scanning electron microscopy also displayed the same tendency.The order of expression of ET-1 RNA was thoracic aorta 〉 carotid artery 〉 femoral artery,and that of eNOS was in contrary.After G-CSF injection,the large artery endothelial morphology and function were affected severely,but the change was much less in small arteries.Conclusions High_fat feeding in rabbits can successfully develop atherosclerosis animal model with severe endothelial dysfunction and morphological alteration.Such changes are more serious in larger artery that indicate the endothelial morphology is closely related with their function,leading to varying responses to G-CSF treatment.
关 键 词:高脂喂养 动脉粥样硬化 内皮形态 内皮功能 粒细胞集落刺激因子
分 类 号:R543.4[医药卫生—心血管疾病]
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