【作者】 卢全；

【导师】 柯元南；

【作者基本信息】 中国协和医科大学 ， 心血管内科学， 2008， 博士

【摘要】 目的:探讨血管紧张素转换酶抑制剂（ACEI）对ApoE基因敲除小鼠动脉粥样硬化病变进展的影响,特别是对斑块成分的影响,并比较培哚普利与依那普利疗效的差别。方法:ApoE基因敲除小鼠随机分为培哚普利组、依那普利组及对照组3组。对主动脉根部斑块进行定量分析,并评估斑块胶原含量及脂核面积。以冰冻切片进行免疫荧光检查,观察斑块内单核细胞/巨噬细胞-2（MOMA-2）、细胞间粘附分子-1（ICAM-1）、血管细胞粘附分子-1（VCAM-1）、基质金属蛋白酶-9（MMP-9）的表达。结果:各实验组之间的血压、血脂无显著性差别。与对照组比较,培哚普利组与依那普利组的斑块面积分别减少了25.33%和22.86%（P均＜0.01）,但是两组ACEI的斑块面积差异无统计学意义。培哚普利组与依那普利组减小脂核面积（分别为52.98%及38.98%,P均＜0.01）及MOMA-2（分别为88.38%及52.16%,P均＜0.01）、ICAM-1（分别为80.87%及49.59%,P均＜0.01）、VCAM-1（分别为77.56%及56.44%,P均＜0.01）、MMP-9（分别为86.93%及55.56%,P均＜0.01）的表达,并增加斑块胶原含量（分别为298.36%及168.14%,P均＜0.01）,而且培哚普利组在这些方面均显著优于依那普利组（P均＜0.05）。结论:ACEI在不影响血脂和血压的情况下可以抑制ApoE基因敲除小鼠动脉粥样硬化斑块的炎症并延缓动脉粥样硬化的进展。尽管培哚普利和依那普利在减少斑块面积方面差异无统计学意义,但是培哚普利在稳定斑块方面优于依那普利。目的:探讨培哚普利对ApoE基因敲除小鼠冠状动脉和主动脉根部动脉粥样硬化进展的影响。方法:20只ApoE基因敲除小鼠随机分为培哚普利组(1-5mg.kg^-1.d^-1,n=10)及对照组（生理盐水,0.2ml/d,n=10）,20周后处死小鼠。切片以改良Movat五色套染法染色后,对冠状动脉和主动脉根部斑块面积进行定量分析。结果:与对照组比较,培哚普利组的冠状动脉斑块面积（分别为81599±6041μm²及65718±5059μm²,P＜0.01）和主动脉根部斑块面积（分别为937678±90445μm²及700148±72537μm²,P＜0.01）明显减少。对照组的冠状动脉斑块面积与主动脉根部斑块面积呈正相关（r=0.791,P＜0.01）,培哚普利组的冠状动脉斑块面积与主动脉根部斑块面积也呈正相关（r=0.721,P＜0.05）。结论:培哚普利既减少冠状动脉斑块的面积,也减少主动脉根部斑块的面积。冠状动脉斑块面积与主动脉根部斑块面积密切相关。更多还原

【Abstract】 ObjectiveTo investigate the effects of angiotensin converting enzyme（ACE） inhibitors on the development of atherosclerotic lesions,particularly on the composition of plaque,in ApoE knockout mice,and to compare the different effects between perindopril and enalapril.MethodsApoE knockout mice were treated with perindopril(1.5mg·kg^-1·d^-1, n=20),or enalapril(7.5 mg·kg^-1·d^-1,n=20)or saline（0.2 ml/d,n=20） per gavage for 20 weeks.Blood pressure and lipids were measured at the study end.Aortic root atherosclerotic plaque was then quantified and the content of collagen and the size of lipid core in the plaque were assessed. Cryostat sections were used to quantify the expressions of monocyte/macrophage-2（MOMA-2）,intercellular adhesion molecule-1 （ICAM-1）,vascular cell adhesion molecule-1（VCAM-1） and matrix metalloproteinases-9（MMP-9） in the plaque by immunofluorescence method. ResultsBlood pressure and lipid profiles were similar among different groups.Compared with control group,the plaque areas of perindopril group and enalapril group displayed significant decrease（25.33%and 22.86%,respectively,both P＜0.01）.However,no significant differences were observed in the plaque size between the different ACE inhibitor groups.It was demonstrated that in perindopril group and enalapril group the size of lipid core significantly decreased（52.98%and 38.98%, respectively,both P＜0.01） and the expression of MOMA-2（88.38%and 52.16%,respectively,both P＜0.01）,ICAM-1（80.87%and 49.59%, respectively,both P＜0.01）,VCAM-1（77.56%and 56.44%,respectively, both P＜0.01） and MMP-9（86.93%and 55.56%,respectively,both P＜0.01） also significantly decreased,and the plaque collagen content increased significantly（298.36%and 168.14%,respectively,both P＜0.01） and the effects of perindopril were superior to those of enalapril（all P＜0.05）.ConclusionsACE inhibitors significantly suppressed tissue inflammation and attenuated the development of atherosclerosis in ApoE knockout mice independent of their effects on the lipid and blood pressure.Perindopril is superior to enalapril in stabilizing the plaques and has similar effect on reducing the plaque size as that of enalapril. ObjectiveTo investigate the effects of perindopril on the development of atherosclerotic lesions in coronary artery and aortic root of ApoE knockout mice.MethodsTwenty ApoE knockout mice were randomly divided into two groups:perindoprilor group(1.5mg·kg^-1·d^-1,n=10) and control group （saline,0.2 ml/d,n=10）.These mice were sacrificed after 20 weeks.The plaque areas of coronary artery and aortic root were measured after the sections were stained with a modified Movat pentachrome stain.ResultsCompared with control group,plaque areas of coronary artery （81599±6041μm² and 65718±5059μm²,respectively,P＜0.01） and aortic root（937678±90445μm² and 700148±72537μm²,respectively, P＜0.01） in perindopril group were significantly decreased.The plaque areas of coronary artery were positively correlated with the plaque areas of aortic root in perindopril group（r=0.791,P＜0.01）.The plaque areas of coronary artery were also positively correlated with the plaque areas of aortic root in control group（r=0.721,P＜0.05）.ConclusionsPerindopril not only decreases plaque areas of coronary artery but also decreases plaque areas of aortic root.The plaque areas of coronary artery are closely correlated with the plaque areas of aortic root.更多还原