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目的研究酰基辅酶A:胆固醇酰基转移酶-1(ACAT-1)和过氧化体增殖物激活型受体γ(PPAR-γ)在动脉粥样硬化斑块中的表达,以及血管紧张素Ⅱ1型受体拮抗剂缬沙坦对ACAT-1和PPAR-γ表达的影响。方法24只雄性日本大耳白兔随机分为对照组、缬沙坦干预组和高胆固醇饮食组,每组8只。喂养12周后,抽取静脉血检测血脂水平,并进行主动脉内膜/中膜比值测定,以RT-PCR和Western blotting方法检测各组主动脉ACAT-1、PPAR-γ mRNA及蛋白的表达。结果高胆固醇饮食组及缬沙坦干预组的血清胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)均无差别(P>0.05),但均高于对照组(P<0.01)。高胆固醇饮食组内膜和内膜/中膜厚度比值显著高于对照组和缬沙坦干预组(P<0.01,P<0.05),而缬沙坦干预组内膜和内膜/中膜厚度比值显著高于对照组(P<0.01)。与对照组比较,高胆固醇饮食组和缬沙坦干预组ACAT-1、PPAR-γ mRNA和蛋白含量显著增加(P<0.01或P<0.05);ACAT-1 mRNA和蛋白在缬沙坦干预组的表达显著低于高胆固醇饮食组(P<0.01或P<0.05),而PPAR-γ mRNA和蛋白在缬沙坦干预组的表达显著高于高胆固醇饮食组(P<0.05)。高胆固醇饮食组和缬沙坦干预组ACAT-1和PPAR-γ mRNA的表达呈明显负相关(P<0.05)。结论缬沙坦可能通过上调PPAR-γ抑制ACAT-1的表达,从而起到抗动脉粥样硬化的作用。
Objective To investigate the expression of acyl-CoA: ACAT-1 and PPAR-γ in atherosclerotic plaques and the relationship between angiotensin Ⅱ type 1 Effect of receptor antagonist valsartan on the expression of ACAT-1 and PPAR-γ. Methods Twenty-four male Japanese white rabbits were randomly divided into control group, valsartan intervention group and high cholesterol diet group, with 8 in each group. Blood samples were taken for venous blood for 12 weeks. The aorta intima / media ratio was measured. The expressions of ACAT-1 and PPAR-γ mRNA and protein were detected by RT-PCR and Western blotting. Results There was no difference in serum cholesterol, triglyceride and low density lipoprotein cholesterol (LDL-C) between the high cholesterol diet group and the valsartan intervention group (P> 0.05), but both were higher than those in the control group (P <0.01). The ratio of intima to intima / media thickness in high cholesterol diet group was significantly higher than that in control group and valsartan intervention group (P <0.01, P <0.05), while in valsartan intervention group, intima and intima / media thickness Ratio was significantly higher than the control group (P <0.01). Compared with the control group, the mRNA and protein levels of ACAT-1 and PPAR-γ in the high-cholesterol diet group and the valsartan intervention group were significantly increased (P <0.01 or P <0.05); ACAT-1 mRNA and protein in the valsartan intervention group (P <0.01 or P <0.05), while the expression of PPAR-γ mRNA and protein in valsartan intervention group was significantly higher than that of high cholesterol diet group (P <0.05). The expression of ACAT-1 and PPAR-γ mRNA in high cholesterol diet group and valsartan intervention group was negatively correlated (P <0.05). Conclusion Valsartan may inhibit the expression of ACAT-1 by up-regulating PPAR-γ, which may play an anti-atherosclerotic effect.