阿托伐他汀对自发性高血压大鼠细胞色素P450羟化酶基因表达的影响

Effects of atorvastatin on expression of cytochrome P450 hydroaylase in spontaneously hypertensive rats

目的:评价阿托伐他汀对自发性高血压大鼠(SHR)血压和细胞色素P450羟化酶(CYP)4A1的调节作用。方法:18只SHR随机分为3组:SHR对照组、阿托伐他汀50mg组(HATV组)和10mg组(LATV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);RT-PCR、Western blotting法检测心、肝、肾及主动脉中CYP4A1 mRNA和蛋白质表达;并测定血脂含量。结果:用药前SHR各组SBP均显著高于WKY组(P<0.01);HATV组在给药后第6、8、10周和LATV组在给药后第10周SBP明显低于SHR对照组(P<0.05或P<0.01)。在CYP4A1 mRNA及其蛋白质表达中,SHR对照组4种组织均明显高于WKY组(P<0.01或P<0.05);给药10周后,HATV组心、肾及主动脉和LATV组肾和主动脉的表达均明显低于SHR对照组(P<0.01或P<0.05);同时,用药2组血脂水平亦明显低于SHR对照组(P<0.01或P<0.05)。结论:阿托伐他汀可下调CYP4A1基因的表达,这可能是其降低血压的作用机制之一。

AIM： To investigate the effects of atorvastatin on blood pressure and expression of cytochrome P450 hydroaylase （CYP） 4A1 in spontaneously hypertensive rats （ SHR ）. METHODS ： SHRs （ n = 18 ） were randomly divided into three groups： SHR control group, 50 mg atorvastatin （HATV） group and 10 mg （LATV） group. Six male Wistar- Kyoto rats were selected as normal control group （ WKY group）. All rats were given vehicle once a day by garage for 10 weeks. Systolic blood pressure （SBP） was measured before and after treatment every 2 weeks. The expressions of CYP 4A1 mRNA and protein in heart, liver, kidney, and aorta were detected by RT -PCR and Western blotting analysis, 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 HATV group at 6, 8, 10 weeks and in LATV group merely at 10 weeks （P 〈0. 01 or P 〈 0. 05 ）. The expressions of CYP 4A1 mRNA and protein in heart, liver, kidney and aorta tissues of SHR control group were significantly higher than those in WKY group （P〈0. 01 or P〈0.05）. After 10 weeks, the levels of CYP 4A1 mRNA, protein and plasma lipids in HATV and LATV groups were markedly lower than those in SHR control group （ P 〈 0.01 or P 〈 0. 05 ）. CONCLUSION： Atorvastatin down - regulates the expressions of CYP 4A1 mRNA and protein in SHR, which may be the mechanism of the favorable effects of statins on regulation of hypertension.