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

目的:观察高脂血症时动脉血管紧张素Ⅱ1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20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。

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

AIM:To study the impact of hyperlipidemia on aortic AT₁ mRNA expression and vasoactive substances, and investigate the potential mechanism on reversion of endothelial dysfunction during the statin therapy.METHODS:The investigation included control, hyperlipidemic and simvastatin-treated groups. Hyperlipidemic model was set up on the 4-week atherogenic diet, followed by a 16-week treatment in the simvastatin treated group (simvastatin 10 mg·kg^-1·d^-1) and without treatment in the hyperlipidemic group. Serum lipid level, the expression of AT₁mRNA of aorta and level of serum AngⅡ and nitric oxide (NO) were measured. RESULTS: Compared with the control group, hyperlipidemic rats showed a stronger expression of AT₁ mRNA and lower level of NO. No significant difference in systolic blood pressure and AngⅡ was showed in this group. In contrast, in simvastatin treated group, expression of AT₁ mRNA as well as lipid(TC, TG, LDL-C) levels were significantly decreased and NO level increased which associated with improvement of endothelial dysfunction. CONCLUSION:By regulated the lipid level, downregulated AT₁ mRNA expresstion and increased the NO activity, simvastatin restored endothelial function and inhibited atherogenesis.