Lu Quan, Ke Yuan-nan, Cheng Wen-li, Wang Yong, Yu Chang-an, Wen Jian-yan
Postgraduate School of Peking Union Medical College, Beijing 100730, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2008 Apr;36(4):350-4.
To compare the effects of perindopril and enalapril on the development of atherosclerotic lesions in ApoE knockout mice.
ApoE knockout mice were treated with perindoprilor (1.5 mg.kg(-1).d(-1), n = 20), enalapril (7.5 mg.kg(-1).d(-1), n = 20) or saline (0.2 ml 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 the 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.
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 different 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).
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.
比较培哚普利和依那普利对载脂蛋白E基因敲除小鼠动脉粥样硬化病变发展的影响。
对载脂蛋白E基因敲除小鼠分别给予培哚普利（1.5毫克·千克⁻¹·天⁻¹，n = 20）、依那普利（7.5毫克·千克⁻¹·天⁻¹，n = 20）或生理盐水（0.2毫升生理盐水/天，n = 20）灌胃，持续20周。在研究结束时测量血压和血脂。然后对主动脉根部动脉粥样硬化斑块进行定量，并评估斑块中胶原蛋白含量和脂质核心大小。使用低温恒温器切片通过免疫荧光法对斑块中单核细胞/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-1（VCAM-1）和基质金属蛋白酶-9（MMP-9）的表达进行定量。
不同组之间血压和血脂水平相似。与对照组相比，培哚普利组和依那普利组的斑块面积显著减小（分别为25.33%和22.86%，均P < 0.01）。然而，不同ACE抑制剂组之间的斑块大小未观察到显著差异。培哚普利组和依那普利组还显著减小了脂质核心大小（分别为52.98%和38.98%，均P < 0.01）以及MOMA-2（分别为88.38%和52.16%，均P < 0.01）、ICAM-1（分别为80.87%和49.59%，均P < 0.01）、VCAM-1（分别为77.56%和56.44%，均P < 0.01）和MMP-9（分别为86.93%和55.56%，均P < 0.01）的表达，并增加了斑块胶原蛋白含量（分别为298.36%和168.14%，均P < 0.01），且培哚普利的效果优于依那普利（均P < 0.05）。
ACE抑制剂可显著抑制组织炎症并减轻载脂蛋白E基因敲除小鼠动脉粥样硬化的发展，且独立于其对血脂和血压的影响。培哚普利在稳定斑块方面优于依那普利，在减小斑块大小方面与依那普利效果相似。
