肾素抑制剂对兔动脉粥样硬化及斑块炎症的影响

目的 探讨肾素抑制剂阿利吉仑的抗动脉粥样硬化(As)作用及对As炎症的影响.方法 通过高脂饲养建立兔As模型,24只新西兰大白兔随机分为单纯高脂组(n=8)、阿利吉仑组(n=8)和正常对照组(n=8).单纯高脂组以高脂饲料(1.5％胆固醇+5％猪油)喂养,阿利吉仑组在高脂饲料喂养的基础上加阿利吉仑(25 mg·kg-1 ·d-1)喂养,正常对照组以常规颗粒饲料喂养.分组喂养16周,处死动物取胸主动脉标本行组织形态学检查,免疫组织化学法检测斑块内巨噬细胞和平滑肌细胞标志物(RAM11和α-actin)及植物血凝素样氧化低密度脂蛋白受体1(LOX-1)表达,以阳性面积表达率表示.结果 油红O染色组织学检查显示:阿利吉仑组的脂质斑块面积为( 34.38±2.07)％,明显小于单纯高脂组的(47.12±4.16)％(P＜0.01).免疫组织化学检测显示:阿利吉仑组斑块内RAM11和LOX-1蛋白表达阳性细胞百分比分别为(21.13 ±2.10)％和(11.38±1.69)％,均明显小于单纯高脂组的(30.63±2.26)％和(16.75±1.67)％(P＜0.01,P＜0.05).单纯高脂组和阿利吉仑组斑块内均可见α-actin表达阳性的梭形平滑肌细胞,主要分布于内膜及中膜.结论 阿利吉仑抑制了As的进展,具有抗炎症作用.

Effect of renin inhibitor on atherosclerosis and plaque inflammation in rabbits

Objective To investigate the effects of renin inhibitor,Aliskiren on atherosclerosis(As) and As inflammation.Methods Rabbit As model was established by high fat diet,and 24 New Zealand rabbits were randomly divided into single high fat group(n=8),Aliskiren group(n=8) and normal control group(n=8).Rabbits in single high fat group were fed with high fat diet(1.5% cholesterol+5% lard oil),those in Aliskiren group were fed with high fat diet and Aliskiren(25 mg·kg-1·d-1),and those in normal control group were fed with regular diet.Rabbits were fed for 16 weeks,and were sacrificed.Thoracic aorta samples were obtained for histological examination,and immunohistochemistry was used to detect the expression of biomarkers of macrophages and smooth muscle cells(RAM11 and α-actin) and lectin like oxidized LDL receptor-1(LOX-1) in plague,which were indicated as ratios of area of positive expression.Results Histological examination with oil red O staining revealed that the area of plaque in Aliskiren group was significantly lower than that in single high fat group [(34.38±2.07)% vs(47.12±4.16)%,P<0.01].Immunohistochemical detection indicated that the ratios of cells with positive expression of RAM11 and LOX-1 protein in plaque in Aliskiren group were(21.13±2.10)% and(11.38±1.69)% respectively,which were significantly lower than those in single high fat group [(30.63±2.26)% and(16.75±1.67)% respectively](P<0.01,P<0.05).Spindle smooth muscle cells with positive expression of α-actin were observed in plaque in single high fat group and Aliskiren group,which mainly located in intima and media.Conclusion Aliskiren inhibits the progression of As,and reduces inflammatory response in plaque.