Comparison of the inhibitory effects of rosuvastatin and atorvastatin on arterial calcification
Objective To explore the difference in inhibitory effects of rosuvastatin and atorvasta-tin on arterial media calcification and their effects on ratio of osteoprotectin(OPG)and receptor activator of nuclear factor-KB ligand(RANKL).Methods The animal model and cell model of arterial media calcifi-cation were established respectively.The 6-8 weeks old male SD rats,weighing 180-200 g,were purchased from Hunan Silaikejingda Experimental Animal Co.,Ltd.Arterial media calcification animal model was es-tablished by intragastric administration of warfarin in rats,and calcification cell model was established by calcification of rat aortic media smooth muscle cells(SMC)induced by vitamin C and β-glycerol phos-phate.Totally,80 rats were randomly divided into 4 groups using a random number table method:normal control group,calcification group,rosuvastatin group,and atorvastatin group,with 20 rats in each group.Rosuvastatin group and atorvastatin group were treated with rosuvastatin and atorvastatin respectively.Calcium content was measured by spectrophotometer,alkaline phosphatase(ALP)activity was detected by Coomassie brilliant blue method,osteocalcin level was determined by Western blotting,and the expression of OPG and RANKL was detected by real-time quantitative polymerase chain reaction(Real-time PCR).One-way ANOVA was used for comparison between groups,and independent samples t test was used for comparison between two groups.Results In animal models,the calcium ion content,ALP activity,and osteocalcin expression levels in the rosuvastatin group and atorvastatin group were lower than those in the calcification group[(0.94±0.09)mg/g vs.(1.44±0.10)mg/g,34.39±7.68 vs.100.60±5.90,0.51±0.07 vs.0.92±0.09,t=9.926,30.564,16.287,P<0.05;(1.30±0.29)mg/g vs.(1.44±0.10)mg/g,61.47±4.04 vs.100.60±5.90,0.74±0.06 vs.0.92±0.09,t=2.092,24.463,7.528,P<0.05].Compared with the atorvastatin group,calcium ion content,ALP activity,and osteocal-cin expression levels were reduced in the rosuvastatin group[(0.94±0.09)mg/g vs.(1.30±0.2)mg/g,34.39±7.68 vs.61.47±4.04,0.51±0.07 vs.0.74±0.06,t=5.152,13.946,10.887,P<0.05].Compared with the atorvastatin group,the OPG/RANKL ratio of the arteries in the ro-suvastatin group was increased(1.08±0.15 vs.0.77±0.03,t=8.742,P<0.05).In the cell model,the calcium ion content,ALP activity,and osteocalcin expression levels in the rosuvastatin and atorvastatin groups were lower than those in the calcification group[(69.83±3.77)μg/mg protein vs.(133.00±4.50)μg/mg protein,29.42±1.81 vs.99.94±3.83,0.49±0.06 vs.0.92±0.06,t=48.156,74.403,22.931,P<0.05;(99.03±2.93)vs.(133.00±4.50)μg/mg protein,61.14±2.13 vs.99.94±3.83,0.79±0.07 vs.0.92±0.06,t=28.326,39.633,6.610,P<0.05].Compared with the atorvastatin group,calcium ion content,ALP activity,and osteocalcin expression levels were reduced in the rosuvastatin group[(69.83±3.77)μg/mg protein vs.(99.03±2.93)μg/mg protein,29.42±1.81 vs.61.14±2.13,0.49±0.06 vs.0.79±0.07,t=27.363,50.747,15.246,P<0.05].Com-pared with the atorvastatin group,the OPG/RANKL ratio of cells in the rosuvastatin group was increased(1.08±0.09 vs.0.78±0.12,t=9.034,P<0.05).Conclusion Rosuvastatin has more obvious anti-calcification effect than atorvastatin,and its mechanism may be related to its stronger ability to upregulate the OPG/RANKL ratio.