【作者】 刘明； 徐志伟； 周妃妃； 朱宝琦； 金雨虹；

【Author】 Ming LiuZhiwei XuFeifei ZhouBaoqi XuYuhong Jin Intensive Care UnitLihuili Hospital57Xingning RoadNingbo 315040China

【机构】 宁波市医疗中心李惠利医院重症监护科；

【摘要】 目的探讨辛伐他汀抗动脉粥样硬化(AS)作用与其对中心动脉压力作用的相关性。方法野生型组、apoE-/-组、apoE-/-+辛伐他汀组三组各6只小鼠均于5周龄高脂喂养,8周龄予以辛伐他汀(50mg/kg/day)干预。11周龄进行中心动脉压力测量,取材并进行血脂、主动脉根部斑块面积测量。结果野生型组主动脉根部未形成动脉粥样硬化斑块;与apoE-/-组相比,辛伐他汀显著降低了主动脉根部斑块面积((89588±21920)um2比(22793±6939)um2)(P<0.05)。与野生型组比较,其他两组中心动脉血压(包括收缩压、舒张压、平均动脉压和脉压)均明显增高(P均<0.05);与apoE-/-组相比,辛伐他汀明显降低了中心动脉收缩压、平均动脉压和脉压均(P均<0.05),对舒张压虽有降低趋势但无统计学意义((85.09±2.02)mmHg比(79.04±1.48)mmHg)(P>0.05)。中心动脉收缩压(P=0.0461,r=0.7152,n=8)和脉压(P=0.0288,r=0.7594,n=8)与斑块面积成正相关。结论辛伐他汀明显抑制了apoE-/-小鼠动脉粥样硬化的进展,其对中心动脉血压的调节可能在此过程中发挥一定作用。更多还原

【Abstract】 Objective:Recent studies suggested that high mobility group box 1(HMGBl) and receptor for advanced glycation end products(RAGE) contribute to atherosclerosisand statin may inhibit tissue RAGE or increase serum sRAGE.Howeverit remains whether statin suppress HMGBl-RAGE axis in atherosclerosis models.Thusin this studywe tested the hypothesis that simvastatin suppresses HMGBl-RAGE axis and atherosclerosis in apoE deficient mice. Methods:Male apoE deficient mcieage 5 weekswere offered western diet.At age 8 weeksmice were treated with once-daily simvastatin(50mg/kg/day)simvastatin(50mg/kg/day)+mevalonic acid(30mg/kg/day)(SM) or vehicle;all mice were killed at age 11 weeks. Results:Compared with apoE deficient mcie treated with vehicle or SMsimvastatin-treated mice displayed decreased atherosclerosis lesion area in a lipid-independent manner.In parallelit was observed that decreased expression of vascular HMGB1RAGEVCAM-1MCP-1 and TF in apoE deficient mice treated with simvastatin versus vehicle or SM.Furthermoreincreased sRAGE in serum were observed in simvastatin-treated apoE deficient miceand the level of sRAGE was negatively correlated with the serum HMGB1 level and atherosclerosis lesion area.More interestinglyconsistent with the premise that addition of HMGB 1 to HUVECs resulted in increased expression of HMGBIRAGE and VCAM-land simvastatin reverted the effects of HMGBl.The roles of simvastatin were similar to RAGE blockade by anti-RAGE antibody in vitro. Conclusion:Simvastatin suppressed HMGBl-RAGE axis and atherosclerosis via mevalonate pathway.更多还原