缬沙坦对动脉粥样硬化兔核因子κB和单核细胞趋化因子-1的影响

Effects of Valsartan on Nuclear Factor-κB and Monocyte Chemotactic Protein-1 in Experimental Atherosclerosis of Rabbits

目的:探讨血管紧张素Ⅱ1型受体(AT1R)拮抗剂缬沙坦(Val-sartan)对动脉粥样硬化(AS)兔核因子κB(NF-κB)和单核细胞趋化因子-1(MCP-1)的影响。方法:24只雄性日本大耳白兔随机分为3组:正常对照组,AS模型组,缬沙坦治疗组。喂养12周,进行血脂测定、主动脉内膜/中膜比值测定、主动脉NF-κB和MCP-1的表达和蛋白质含量测定。结果:AS模型组NF-κB和MCP-1蛋白含量显著增加(P<0.05),缬沙坦治疗组显著减少(P<0.05),且NF-κB活化和MCP-1表达之间成正相关(r=0.728,P<0.01);缬沙坦治疗组及AS模型组的血清胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)均无差别(P均>0.05),但均高于正常对照组。与AS模型组比较,缬沙坦治疗组主动脉内膜/中膜厚度比值明显减少(P<0.05)。结论:缬沙坦可以干预AS的形成,其机制可能与其抑制NF-κB的活化从而下调MCP-1的表达有关。

Objective:To explore the effects of valsartan on nuclear factor-κB and monocyte chemotactic protein-1 in rabbits with atherosclerosis.Method:24 male Japanese White Rabbits were randomly divided into 3 group:group 1:normal rabbit chow;group 2 cholesterol diet;group 3 cholesterol diet supplemented by Valsatarn.All rabbits were fed according to experiment design for 12 weeks.Blood samples were abstracted from vein for detection of serum lipid.The intima-media thickness were measured.Nuclear Factor-κB(NF-κB) and monocyte chemotactic protein-1(MCP-1) were examined by immunohistochemistry and Western-Blot respectively.Results:After 12 weeks,NF-κB and MCP-1 were significantly increased in aorta of rabbit in group 2(P<0.05).NF-κB and MCP-1 were significantly reduced in aorta of rabbit in group 3.Furthermore,the upregulation of MCP-1 expression was positively correlated with NF-κB activation(r=0.728,P<0.01).Levels of serum TC,TG,LDL in group 2 and 3 were significant higher than those of group 1(P<0.05),but they had not significant difference between group 2 and 3(P>0.05).The ratio of intima-media reduced obviously in group 3 as compared to those of group 2(P<0.05).Conclusion:Valsatarn could intervene with experimental atherosclerotic development in rabbits,which mechanism might be that Valsatarn could affect the NF-κB activation and MCP-1 expression.