缬沙坦的抗动脉粥样硬化作用及其可能机制  

Effects of Valsartan on Atherosclerosis in the Cholesterol-fed Rabbits

作　　者：曾永利[1] 成蓓[1] 马志强[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院综合科,湖北省武汉市430022

出　　处：《中国动脉硬化杂志》2007年第2期105-108,共4页Chinese Journal of Arteriosclerosis

摘　　要：目的研究血管紧张素Ⅱ1型受体拮抗剂缬沙坦对兔动脉粥样硬化病变中过氧化体增殖物激活型受体γ及单核细胞趋化蛋白1和白细胞介素6的影响。方法24只雄性大耳白兔随机分为3组:正常组(n=8),高胆固醇饮食组(1%胆固醇+5%猪油颗粒饲料,n=8),缬沙坦组[10mg/(kg.d),n=8],喂养12周。对各组兔采血进行血脂测定,主动脉内膜/中膜比值测定,采用逆转录聚合酶链反应检测过氧化体增殖物激活型受体γ和单核细胞趋化蛋白1mRNA的表达,采用酶联免疫吸附测定法检测兔血清白细胞介素6的水平。结果缬沙坦组过氧化体增殖物激活型受体γmRNA的表达较高胆固醇饮食组明显增加(1.75±0.23比1.12±0.16,P<0.05),缬沙坦组单核细胞趋化蛋白1mRNA的表达较高胆固醇饮食组明显减少(1.14±0.22比1.95±0.32,P<0.05)。缬沙坦组白细胞介素6水平较高胆固醇饮食组明显减少(32.42±6.12比83.73±5.42ng/L,P<0.05)。缬沙坦组内膜/中膜厚度比值较高胆固醇饮食组明显减少(P<0.05)。缬沙坦组及高胆固醇饮食组的血清胆固醇、甘油三酯、低密度脂蛋白胆固醇差异无显著性,但均明显高于正常组(P<0.01)。结论缬沙坦抑制兔动脉粥样硬化主动脉单核细胞趋化蛋白1的表达和血清白细胞介素6水平,其机制可能是增加过氧化体增殖物激活型受体γmRNA表达有关。Aim To study the effect of Valsartan on the mRNA expression of peroxisome proliferator-activated receptor gamma （PPARγ） and monocyte chemoattractant protein-1 （MCP-1） and the secretion of interleukin-6（IL-6） in experimental atheroselerotic rabbits. Methods Male Japanese White Rabbits were randomly divided into three groups： control group, cholesterol group, Valsartan group. All rabbits were fed according to experiment design for 12 weeks. Blood samples were taken from vein for detection of serum lipid. The intima-media thickness was measured. PPARγ and MCP-1 were examined by reverse transcription polymerase chain reaction. IL-6 in serum was evaluated by ELISA. Results The expression of PPARγ mRNA was higher in Valsartan group than cholesterol group（1.75±0.23vs1.12±0.16, P〈0.05）. The expression of MCP-1 mRNA was lower in Valsartan group than cholesterol group（1.14±0.22vs1.95±0.32, P〈0.05）. The levels of IL-6 was lower in Valsartan group than cholesterol group （32.42±6.12vs83.73±5.42ng/L, P 〈0.05）. The rafio of intima-media reduced obviously in Valsartan group than those of cholesterol group （ P 〈 0.05 ）. Levels of serum TC, TG, LDL-C in cholesterol group and Valsartan group were significant higher than those of control group （ P 〈 0.01 ）, but they had not significant difference between cholesterol group and Valsartan group. Conclusions Valsartan could inhibit the MCP-1 mRNA expression and IL-6 level by increasing PPARγ mRNA expression in experimental atheroselerotic rabbits.

关 键 词：缬沙坦 过氧化体增殖物激活型受体Γ 单核细胞趋化蛋白1 白细胞介素6 动脉粥样硬化 

分 类 号：R543.5[医药卫生—心血管疾病] R972[医药卫生—内科学]