摘要
目的:研究血管紧张素Ⅱ1型受体拮抗剂缬沙坦对实验性兔动脉粥样硬化形成,以及对主动脉单核细胞趋化蛋白-1(MCP-1)和过氧化物酶体增殖物激活受体γ(PPARγ)的影响。
方法: 24只雄性新西兰白兔随机分为3组:对照组,动脉粥样硬化(AS)造模组,缬沙坦组,喂养12周。进行血脂测定,主动脉内膜/中膜比值测定,免疫组化方法检测各组主动脉MCP-1和PPARγ蛋白,RT-PCR检测MCP-1和PPARγmRNA的表达。
结果:缬沙坦组及AS造模组的血清胆固醇、甘油三酯、低密度脂蛋白胆固醇均无差异(各P>0.05) ,但均高于对照组(P<0.01)。缬沙坦组内膜/中膜厚度比值较AS造模组明显减少(P<0.05)。AS造模组动脉粥样硬化血管组织MCP-1蛋白和mRNA的表达较对照组明显增多(P<0.05),而缬沙坦组动脉粥样硬化血管组织MCP-1蛋白和mRNA的表达较AS造模组明显减少(P<0.05),缬沙坦组动脉粥样硬化血管组织PPARγ蛋白和mRNA的表达较AS造模组明显增加(P<0.05)。
结论:缬沙坦抑制兔动脉粥样硬化形成,并抑制动脉粥样硬化血管MCP-1,说明它具有抗炎作用,其抗炎作用可能与其增加动脉粥样硬化血管组织PPARγ有关。
Objective: To study the effect of Valsartan on the expression of monocyte chemoattractant protein-1(MCP-1) and peroxisome proliferator activated receptor gamma (PPARγ) in experimental atherosclerotic rabbits.
Methods: Twenty four male New Zealand rabbits were randomly divided into 3 group : group 1: normal rabbit chow, group 2: cholesterol diet, group 3: cholesterol diet supplemented by Valsartan. All rabbits were fed according to experiment design for 12 weeks. Blood samples were obtained from vein for detection of serum lipid. The intima-media thickness was measured. The expression of MCP-1 and PPARγwere examined by immunohistochemistry and reverse transcription polymerase chain reaction.
Results: Levels of serum TC、TG、LDL-C in group 2 and 3 were significant higher than those of group 1(P<0.05), but it has no significant difference between group 2 and 3 (P>0.05). The ratio of intima-media reduced obviously in group 3 than those of group 2 (P<0.05). The expression of MCP-1 was higher in group 2 than group 1 and group3 (P<0.05). The expression of PPARγwas higher in group 3 than group 2(P< 0.05). Conclusion: These findings suggest that Valsartan could affect atherosclerosis and the MCP-1 expression in experimental atherosclerotic rabbits which are probably related to its activating effect of PPARγ.
引文
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