为探讨瑞舒伐他汀钙(rosuvastatin)对高尿酸血症大鼠模型及其内皮功能紊乱的影响,将72只Sprague-Dawley(SD)雄性大鼠随机分组,采用酵母膏和氧嗪酸钾腹腔注射方法,建立高尿酸血症动物模型.设别嘌呤醇干预为阳性对照,以2.5、5.0和10.0mg瑞舒伐他汀钙/kg剂量干预动物模型,采用专用试剂盒测定尿酸(UA)、一氧化氮(NO)、内皮素-1(ET-1)、血管紧张素II(AngII)的血清水平,免疫组织化学鉴定主动脉组织的一氧化氮合酶(eNOS)蛋白质表达水平变化.结果显示,与对照组比较,高尿酸血症动物模型组血清UA、ET-1和AngII显著升高,血清NO降低,主动脉内皮组织eNOS表达水平降低.瑞舒伐他汀钙干预动物模型后发现,随着药物剂量和干预时间的增加,该药改善以上内皮功能紊乱相关的指标,使之逐渐恢复至正常水平,当瑞舒伐他汀钙干预剂量为10mg/(kg·d)和干预6周时,与非药物干预的模型组有显著差异,其改善内皮功能效果明显高于嘌呤组(阳性对照组).由此表明,瑞舒伐他汀钙通过升高血清中NO和eNOS的蛋白表达,降低血浆ET-1及AngII,从而改善高尿酸血症大鼠的血管内皮功能,并且该作用呈剂量依赖性.
To study the effect of rosuvastatin on hyperuricemia rats and their endothelial dysfunction. 72 male SD rats were randomly grouped, and a hyperuricemia animal model was established by intraperitoneal injection of yeast extract and oxonic acid potassium salt. By setting up the treatment with allopurinol as positive control, the hyperuricemia rats were treated with various doses of rosuvastatin, the levels of Uric Acid (UA), Nitric Oxide (NO), Endothelin 1 (ET-1) and Angiotensin II (Ang II) were detected in serum using commercially available detection kits and the protein expression level of endothelial NO synthase (eNOS) was detected in tissue specimens of aorta by immunohistochemistry. The results show that, compared to the normal control, the serum levels of UA, ET-1 and Ang II of hyperuricemia rats are increased while the serum level of NO and the eNOS expression in tissue specimens of aorta, as an important profile for altered endothelial function of the experimental animal model are decreased. After treatment of the animal model with rosuvastatin, it is found that the drug has improved the profile of endothelial function, which has gradually recovered to the normal level, and the curative effect is significantly higher than the allopurinol group (positive control) at the dosage of 10mg/(kg·d) and intervention time of 6 weeks, as compared to the normal control group, with significant differences from the animal model without treatment. The results suggest that the rosuvastatin treatment can improve the profile of endothelial function via recovering the serum levels of ET-1, Ang II and NO, eNOS induced by hyperuricemia, and the effect is enhanced in a dose-dependent manner.
