阿托伐他汀对动脉中膜钙化及骨保护素/核因子-κB配体的受体的影响

The effect of atorvastatin on the arterial calcification and osteoprotegerin/receptor activator of nuclear factor-κB ligand

目的 观察他汀类药物对动脉中膜钙化的作用及其对骨保护素（OPG）/核因子（NF）-κB配体的受体（RANKL）系统的影响.方法 分别构建钙化的细胞模型和动物模型,每组均分为钙化组、他汀组和对照组.钙化细胞模型中使用β-磷酸甘油、维生素C对大鼠主动脉中膜平滑肌细胞（SMC）进行诱导钙化,他汀组在加入以上物质的同时再加入阿托伐他汀;钙化动物模型中使用华法令对普通大鼠进行灌胃诱导钙化,他汀组使用华法令的同时再加入阿托伐他汀;用钙离子含量测定,碱性磷酸酶（ALP）活性检测,骨钙素的Western blot检测来判定和动脉和细胞钙化的程度,用实时定量聚合酶链反应（Real-time PCR）检测此过程中OPG、RANKL的表达.结果 加入他汀类药物后,动脉和细胞钙化的程度均有所减轻（钙离子含量、ALP活性、骨钙素在动物组中分别由（1.39±0.04） mg/g、72.46±14.78、1.05±0.05降到了（1.01±0.03） mg/g、48.39±9.27、0.56±0.04;在细胞组中分别由（120.66±7.63） μg/mg protein、98.02±9.56、0.95±0.03降到了（95.57±8.47） μg/mg protein、65.34±8.16、0.65±0.02,P＜0.05）,同时动脉和细胞中OPG/RANKL的比值也明显上升（P＜0.05）.结论 他汀类药物具有抑制动脉钙化的作用,其机制可能与其提高OPG/RANKL的比值有关.

Objective To study the function of statins on the arterial calcification and its effect on the osteoprotegerin/receptor activator of nuclear factor-κB （NF-κB） ligand （RANKL）.Methods To constitute the calcified animal and cell models respectively,and each model was divided randomly into the calcified group,statins group,and control group.In the cell model,for the calcified group,β-glycerophosphate and Vitamin C was added into the culture medium,the statins group was given both β-glycerophosphate,Vitamin C and atorvastatin;In the animal model,the calcified group was taken the intragastric administration with Warfarin,the statins group was taken the intragastric administration with both Warfarin and atorvastatin.Ca2＋ content assay,alkaline phosphatase （ALP） activity assay and osteocalcin assayed with WestemBlot were used to check the level of animal and cell calcification;real-time quantitative polymerase chain reaction （Real-time PCR） was used to check the expression of osteoprotegerin （OPG） and RANKL.Results After stastins was added,the level of animal and cells calcification decreased （In the animal model,the Ca2＋ content,ALP activity,osteocalcin decreased respectively from （1.39 ± 0.04） mg/g,72.46±14.78,1.05±0.05 to （1.01 ±0.03） mg/g,48.39±9.27,0.56±0.04;and in the cell model from （120.66±7.63）μg/mgprotein,98.02 ± 9.56,0.95 ±0.03 to （95.57± 8.47） μg/mg protein,65.34 ± 8.16,0.65 ± 0.02 in the cell model,all P 〈 0.05）,and the ratio of OPG/RANKL increased obviously （all P 〈 0.05）.Conclusion Statins could inhibit the arterial calcification,the mechanism was probably connected with its function of increasing ration of OPG/RANKL.