辛伐他汀对高脂血症大鼠动脉血管紧张素Ⅱ1型受体mRNA表达的下调作用

Downregulation of aortic angiotensin II type 1 receptor mRNA e xpression by simvastatin in hyperlipidemic rats

目的 :观察高脂血症时动脉血管紧张素Ⅱ 1型受体 (AT1)mRNA表达水平、外周血血管活性物质的变化特点及降脂治疗的作用 ,探讨辛伐他汀逆转内皮功能障碍的机制。方法 :实验包括正常对照组 ,另两组通过 4周建立高脂血症模型 ,此后继续高脂喂养 ,其中辛伐他汀治疗组在高脂喂养同时喂服辛伐他汀 10mg·kg-1·d-1)而高脂血症组不予药物治疗 ,第 2 0周检测 3组的血脂变化及观察AT1mRNA表达水平、外周血AngⅡ和NO浓度。结果 :高脂血症组AT1mRNA表达水平高于、血NO水平低于正常对照组、而AngⅡ和收缩压无显著差异。辛伐他汀治疗组总胆固醇 (TC)、甘油三脂 (TG)、低密度胆固醇 (LDL -C)显著低于高脂血症组 ,且动脉组织AT1mRNA表达水平也显著低于高脂血症组 ,血NO含量高于高脂血症组、但血AngⅡ浓度和收缩压未见显著差异。结论 :辛伐他汀在调脂的同时 ,下调AT1mRNA的表达、促进一氧化氮的生成 ,从而逆转内皮功能障碍、阻止动脉硬化进展。

AIM: To study the impact of hyperlipidemia on aortic AT 1 mRNA expression and vasoactive substances, and investigate the pot ential mechanism on reversion of endothelial dysfunction during the statin thera py.METHODS: The investigation included control, hyperlipidemic a nd simvastatin-treated groups. Hyperlipidemic model was set up on the 4-week ath erogenic diet, followed by a 16-week treatment in the simvastatin treated group (simvastatin 10 mg·kg -1 ·d -1 ) and without treatment in the hy perlipidemic group. Serum lipid level, the expression of AT 1mRNA of aorta and level of serum AngⅡ and nitric oxide (NO) were measured. RESULTS: Compared with the control group, hyperlipidemic rats showed a stronger expr ession of AT 1 mRNA and lower level of NO. No significant difference in systol ic blood pressure and AngⅡ was showed in this group. In contrast, in simvastati n treated group, expression of AT 1 mRNA as well as lipid(TC, TG, LDL-C) levels were significantly de cr eased and NO level increased which associated with improvement of endothelial dy sfunction. CONCLUSION: By regulated the lipid level, downregulat ed AT 1 mRNA expresstion and increased the NO activity, simvastatin restored en dothelial function and inhibited atherogenesis.