辛伐他汀对急性冠脉综合征病人血管内皮功能保护作用的时效及量效关系探讨

Time-effect and Dose-effect Relationship of Simvastatin for Protecting Endothelial Function

目的探讨中小剂量他汀类药物的血管内皮功能保护作用。方法选择因有典型临床症状而收住院的急性冠脉综合征(ACS)病人85例,采用随机、单盲、对照、自身配对设计的研究方法分为4组,对照组仅给予常规治疗及低脂饮食;辛伐他汀低、中、高剂量组分别在常规治疗基础上给予辛伐他汀片20mg/d,40mg/d,80mg/d,每晚睡前服用,治疗8周。服药0周、4周、8周及停药2周时分别检测内皮素-1(ET-1)、一氧化氮(NO)、肱动脉血管内皮依赖性舒张功能(FMD)和非血管内皮依赖性舒张功能(NMD)指标。结果辛伐他汀各治疗组与治疗前及对照组相比具有明显降低ET-1及升高NOFMD的作用(P<0.05),作用最佳者为80mg组,40mg组次之,20mg组再次之,停药2周,各指标均有所恢复,但与治疗前比较,80mg组尚存轻度降低ET-1的作用。结论不同剂量辛伐他汀具有血管内皮保护作用,短期内存在时间-剂量依赖关系,但随着用药时间的延长这种依赖关系削弱。

Objective To investigate the effect of moderate and low dose of sestatin on protecting endothelial function in patients with acute coronary syndrome. Methods Eightyfive patients with acute coronary syndrome were enrolled consecutively and divided randomly into four groups： Control group （n = 20） treated by general therapeutics for 8 weeks, simvastatin 1 （n = 23, 20 mg/day）, simvastatin 2 （n = 21, 40 mg/day）, simvastatin 3 （n = 21, 80 mg/day）. Endothelin- 1（ET- 1）, Nitric- oxide（NO）, endothelium- dependent vasodilation function and non - endothelium - dependent vasodilatation function in brachial artery were examined by high resolution ultrasound at admission and 4,8,10 weeks after treatment. Results The serttm levels of ET- 1 were decreased and NO, FMD were increased more significantly in statin groups after treatment（P〈 0.05）. There were not different on NMD among various statin groups and between before and af- ter statin：treatment（P 〉0.05）. Conclusion There were time- dependent and dose- dependent features for protecting endothelial function bv simvastatin.