匹伐他汀对高尿酸血症大鼠血尿酸、炎症因子、血管内皮功能的影响

Effects of pitavastatin on serum uric acid,inflammatory factors and vascular endothelial function in hyperuricemia rats

目的:探讨匹伐他汀对高尿酸血症大鼠血尿酸、炎症因子、血管内皮功能的影响。方法:将60只大鼠根据随机数字表法分为对照组(C组)、模型组(M组)、匹伐他汀低剂量组(LP组)、匹伐他汀高剂量组(HP组),每组15只。采用盐酸乙胺丁醇+酵母膏建立高尿酸血症模型。LP组和HP组分别灌胃给予匹伐他汀0.21 mg/(kg·d)和0.42 mg/(kg·d)。ELISA法测定血尿酸、TNF-α、IL-6、NO水平,免疫透射比浊法测定血清C反应蛋白(CRP),放射免疫法测定血内皮素-1(ET-1),HE染色观察主动脉病理变化,免疫组化染色测定主动脉中血管细胞黏附分子-1(VCAM-1)蛋白表达。结果:与C组比较,M组血尿酸水平升高(P<0.05),血清TNF-α、IL-6、CRP水平升高(P<0.05),NO水平降低(P<0.05),ET-1水平升高(P<0.05);与M组比较,LP组和HP组血尿酸水平降低(P<0.05),血清TNF-α、IL-6、CRP水平降低(P<0.05),NO水平升高(P<0.05),ET-1水平降低(P<0.05),主动脉VCAM-1平均吸光度值降低(P<0.05);与LP组比较,HP组各指标变化更显著(P<0.05)。C组大鼠主动脉内皮正常;M组大鼠主动脉内皮细胞肿胀;LP组和HP组大鼠主动脉内皮细胞肿胀明显减轻,其中HP组大鼠主动脉内皮细胞肿胀减轻更为显著。结论:匹伐他汀可降低高尿酸血症大鼠血尿酸水平、降低炎症因子水平、改善血管内皮功能障碍。

Objective:To investigate effects of pitavastatin on serum uric acid,inflammatory factors and vascular endothelial function in hyperuricemia rats.Methods:60 rats were divided into control group(C group),model group(M group),pitavastatin low dose group(LP group) and pitavastatin high dose group(HP group) accorded to random number method.15 rats in each group.The model of hyperuricemia was established used ethambutol hydrochloride + yeast extract.The rats of LP group and HP group were given pitavastatin 0.21 mg/(kg·d) and 0.42 mg/(kg·d) gavage treatment,respectively.The serum uric acid,TNF-α,IL-6 and NO were determined by ELISA.The serum C-reactive protein(CRP) was determined by immunoturbidimetry assay.The blood endothelin-1(ET-1) was determined by radioimmunoassay,Hematoxylin-Eosin(HE) staining were used to observe aortic pathological changes,Immunohistochemical staining was used to determine the expression of vascular cell adhesion molecule-1(VCAM-1) protein in the aorta.Results:Compared with C group,blood uric acid level were increased(P<0.05),serum TNF-α,IL-6,CRP levels were increased(P<0.05),NO level was decreased(P<0.05),ET-1 level was increased(P<0.05) in group M.Compared with group M,serum uric acid levels were decreased(P<0.05),serum TNF-α,IL-6,CRP levels were decreased(P<0.05),NO level was increased(P<0.05),ET-1 level was decreased(P<0.05),the average absorbance of aortic VCAM-1 was decreased(P<0.05) in LP group and HP group;compared with the LP group,the changes of each index in the HP group were more significant(P<0.05).In C group,rats had normal aortic endothelium;in M group,rat aortic endothelial cells were swollen;in LP group and HP group,rats aortic endothelial cell swelling was significantly reduced,among them,the swelling of aortic endothelial cells in HP group was more significant.Conclusion:Pitavastatin can reduce blood uric acid levels,reduce inflammatory factors and improve endothelial dysfunction in hyperuricemia rats.