培哚普利和依那普利对ApoE基因敲除小鼠动脉粥样硬化进展的影响

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程的影响,特别是对斑块成分的影响,并比较培哚普利与依那普利的疗效.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)、细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子(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、血脂差异无统计学意义.与对照组比较,培哚普利组与依那普利组的斑块面积分别少了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.

Effects of perindopril and enalapril on atherosclerosis development of apolipoprotein E knockout mice

Objective To compare the effects of perindopril and enalapril on the development of atherosclemtic lesions in ApoE knockout mice.Metllods ApoE knockout mice were treated with saline/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 tlle content of collagen and the size of lipid core in the plaque 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.Results Blood pressure and lipid profiles were similar among different groups.Compared with control group,the plaque areas of perindopril group and enalapril group displayed significantly decrease(25.33%and 22.86%,respectively,both P＜0.01).However,no significant difierent were observed in the plaque size between the different ACE inhibitors groups.Perindopril group and enalapril group also significantly decreased the size of lipid core(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), and increased the plaque collagen content(298.36%and 168.14%, respectively,both P＜0.01)and the effects of perindopril was superior to those of enalapril(all P＜0.05).Conclusions ACE 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.