目的：观察氧自由基损害和血管内皮功能失调与高血压发生的关系及瑞舒伐他汀干预的影响。方法将8只Wistar －Kyoto 大鼠（WKY）作为正常对照组；32只自发性高血压（SHR）大鼠，随机分为瑞舒伐他汀低剂量组3．125 mg／（kg· d）、瑞舒伐他汀中剂量组6．25 mg／（kg· d）、瑞舒伐他汀高剂量组12．5 mg／（kg· d）和SHR 对照组，每组8只。给药大鼠分别每日给予不同剂量瑞舒伐他汀＋1 mL蒸馏水灌胃；SHR 对照组给予相同容积的蒸馏水灌胃，测量血压。4周停药，3天后麻醉状态下提取心肌组织，用比色法检测SOD、MDA、NO 的水平，免疫组化法测定ET 的表达，PCR 法测定SODmRNA 的水平。结果自发性高血压大鼠SOD 活力、SODmRNA 表达、NO 含量下降，MDA 含量、ET －1的表达增强，与正常对照组比较，P ＜0．05。瑞舒伐他汀干预后上述指标均有改善（P ＜0．05），且呈剂量相关性。瑞舒伐他汀干预后SHR 大鼠血压下降，但无剂量相关性。结论 SHR 大鼠存在氧化应激反应的增强，瑞舒伐他汀可通过降低氧化应激反应，改善血管内皮功能、降低血压。%Objective To observe the relationship of oxygen free radical damage and endothelial dysfunction with hyperten-sion and the effect of rosuvastatin therapy.Methods Eight Wistar-Kyoto rats ( WKY) were used as normal control group, and thirty-two spontaneously hypertensive rats ( SHR ) were randomly and evenly divided into four groups: low-dose group (3.125 mg/kg· d), mid-dose group (6.25 mg/kg· d), high-dose group (12.5 mg/kg· d) and SHR control group.After treated with oral administration of rosuvastatin and equal volume distilled water ( control group) for 4 weeks, all rats were measured blood pressure, then killed.The levels of SOD,MDA,No and ET-1, SOD mRNA expression in myocardial tissue were detected by colorimetry, immunohistochemistry and RT-PCR.Results Compared with normal con-trol group,the levels of SOD, NO, and SOD mRNA expression decreased, while MDA level and ET -1 expression in-creased in SHR group (P<0.05).All these indexes were improved after rosuvastatin treatment (P<0.05), and with a dose-dependent effect.The blood pressure of SHR decreased after rosuvastatin treatment, without the dose-dependent effect.Conclusions The oxidative stress enhanced in SHR.Rosuvastatin could reduce blood pressure by reducing oxidative stress and improving endothelial function.
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