阿托伐他汀对自发性高血压大鼠血管内皮功能的保护作用

Effects of atorvastatin on endothelium protection in spontaneously hypertensive rats

目的:评价不同剂量阿托伐他汀治疗对自发性高血压大鼠(SHR)血管内皮功能的保护作用。方法:18只SHR随机分为3组:SHR对照组、阿托伐他汀50mg组和10 mg组;6只Wistar-Kyoto大鼠(WKY)作为正常对照组。给药共10周,分别于给药前和给药后每2周测量大鼠尾动脉收缩压(SBP),测定血浆一氧化氮(NO)、血管性假性血友病因子(vWF)及血脂含量。结果:用药前SHR各组SBP均显著高于WKY组(P<0.01);阿托伐他汀50 mg组在给药后第6、8、10周和阿托伐他汀10 mg组在给药后第10周,SBP明显低于SHR对照组(P<0.05或P<0.01)。SHR对照组血浆NO浓度明显低于WKY正常对照组(P<0.01);给药10周后,用药2组血浆NO浓度明显高于SHR对照组(P<0.01或P<0.05)。SHR对照组血浆vWF浓度明显高于WKY正常对照组(P<0.01);给药10周后,用药2组血浆vWF浓度明显低于SHR对照组(P<0.01)。同时,用药2组血脂水平低于SHR对照组(P<0.05或P<0.01)。结论:阿托伐他汀可降低血压,并通过提高血浆NO浓度和降低vWF浓度等机制改善血管内皮功能。

Objective： To investigate the effects of two different dosage of atorvastatin on endothelium protection in spontaneously hypertensive rats （SHR）. Methods： SHRs （n： 18） were randomly divided into three groups （n=6）：SHR control group, 50 mg atorvastatin group and 10 mg group. Six male Wistar-Kyoto rats were selected as normal control group（WKY group）. All animals were given vehicle once a day by gavage for 10 weeks. Systolic blood pressure （SBP） was measured before and after treatment with atorvastatin every 2 weeks. Plasma NO and vWF were measured by nitrate reductase method and double antibodies ELISA,respectively. Plasma lipids were also measured. Results： SBP in all SHR groups was much higher than that in WKY group before experiment （P〈0.01）. Compared with SHR control group,SBP significantly decreased in 50 mg atorvastatin group at 6,8 and 10 weeks and in 10 mg atorvastatin group merely at 10 weeks （P〈0.05 or P〈0.01）. The plasma levels of NO in SHR control group was significantly lower than those in WKY group （P〈0.01）. After 10 weeks,plasma NO levels in 50 mg and 10 mg atorvastatin groups were markedly higher than those in SHR control group （P〈0. 01 or P〈 0.05）. The plasma levels of vWF in SHR control group was significantly higher than those in WKY group （P〈0.01）. After 10 weeks,plasma vWF levels in 50 mg and 10 mg atorvastatin groups were markedly lower than those in SHR control group （P〈0.01）. Plasma lipids in 50 mg and 10 mg atorvastatin groups were lower than those in SHR control group （P〈0.05 or P〈 0.01 ）. Conelusion： Atorvastatin can decrease blood pressure and significantly improve endothelial function in SHR by increasing plasma NO level and decreasing plasma vWF level.