厄贝沙坦对高胆固醇饮食载脂蛋白E基因敲除小鼠动脉粥样硬化斑块及NAD(P)H氧化酶的影响  

Effects of irbesartan on atherosclerosis lesion and NAD(P)H oxidase in high cholesterol-diet apolipoprotein E knock-out mice

作　　者：姚瑞[1] 程翔[1] 廖玉华[1] 陈勇[1] 谢江娇[1] 余娴[1] 丁英俊[1] 唐婷婷[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院心内科,同济医学院心血管研究所心血管免疫实验室,湖北武汉430022

出　　处：《中国药理学通报》2008年第10期1289-1293,共5页Chinese Pharmacological Bulletin

基　　金：国家重点基础研究发展计划(973计划)资助项目(No2007CB512000,2007CB512005);国家自然科学基金资助项目(No30600234)

摘　　要：目的探讨血管紧张素受体拮抗剂(ARB)厄贝沙坦对载脂蛋白E基因敲除(ApoE KO)小鼠动脉粥样硬化斑块及烟酰胺腺嘌呤二核苷酸[NAD(P)H]氧化酶的影响。方法ApoE KO小鼠随机分为普食组、高胆固醇饮食组、高胆固醇饮食+厄贝沙坦组,每组15只,分别予蒸馏水、蒸馏水、厄贝沙坦10mg·kg-1.d-1灌胃12wk。无创血压系统测小鼠血压;内眦动脉取血检测血清胆固醇和甘油三脂水平;冰冻切片光镜下定位主动脉根部,油红O染色评估斑块大小;实时定量PCR和Western blot方法检测主动脉中NAD(P)H氧化酶亚基p47phox和Rac-1表达。结果高胆固醇饮食组小鼠血脂明显升高(P<0.01),且斑块面积明显高于普食组(P<0.01);厄贝沙坦可以明显减小斑块面积(P<0.01),同时还可以降低NAD(P)H氧化酶亚基p47phox和Rac-1表达(P<0.01)。结论血管紧张素受体拮抗剂厄贝沙坦可能通过阻断氧化应激反应抑制动脉粥样硬化发生发展。Aim To investigate the potential effects of an angiotensin type 1 receptor blockers irbesartan on the atherosclerosis lesion and NAD （P）H oxidase in high cholesterol-diet （HCD） apolipoprotein E knockout （ApoE KO） mice. Methods Adult male ApoE KO mice were given normal diet （ND） or HCD and randomized to no treatment group or irbesartan 10 mg · kg^-1 · d^-1 for 12 weeks group. Systolic：blood pressure was measured by a kind of non-invasive tail cuff system in conscious mice. The plasma total cholesterol and triglyceride concentration were measured by autoanalyzer. Atherosclerotic lesion area in aortic root was evaluated by oil red O staining. NAD （P） H oxidase subunits were measured by real-time reverse-transcription polymerase chain reaction （PCR） and Western blot. Results The ApoE KO mice with HCD was associated with a marked increase in plasma lipid levels, atheroselerotie lesion area,as well as the expressions of NAD（P） H oxidase subunits p47^phoX and Rae-1. These changes were suppressed in mice treated with irbesartan 10 mg · kg^-1 · d^-1 for 12 weeks concomitant with HCD administration,with no significant change in systolic blood pressure and plasma lipid levels. Conclusion Irbesartan could attenuate atherosclerosis, and this effect was in part related to inhibition of oxidative stress.

关 键 词：动脉粥样硬化 厄贝沙坦 氧化应激 

分 类 号：R-332[医药卫生] R329.24