强化阿托伐他汀治疗抑制兔颈动脉球囊损伤后蛋白酶活化受体1表达及血管内膜增殖  

Effects of atorvastatin on protease-activated receptor-1 expression and neointimal hyperplasia in rabbits fed with cholesterol-enriched diet after carotid balloon injury

作　　者：林志鸿[1,2] 童保文[3] 许昌声 谢良地 

机构地区：[1]福建医科大学附属第一医院急诊科 [2]福建省高血压研究所,福建福州350005 [3]福建医科大学附属第三医院心血管内科

出　　处：《中华高血压杂志》2014年第12期1144-1149,共6页Chinese Journal of Hypertension

基　　金：福建省教育厅科技计划项目(NCETFJ-0609)

摘　　要：目的探讨强化阿托伐他汀治疗对高脂喂食的新西兰大耳白兔颈动脉球囊损伤后血小板活化产物蛋白酶活化受体1(PAR-1)、血小板聚集及血管内膜增殖的影响。方法雄性新西兰大耳白兔30只,随机分为如下处理:对照、高脂喂食+假手术(单纯高脂组),高脂喂食+球囊损伤(高脂+损伤组)、球囊损伤+阿托伐他汀5mg/(kg·d)治疗(低剂量他汀组)、球囊损伤+阿托伐他汀10mg/(kg·d)治疗(高剂量他汀组),每组6只。比浊法测定血小板聚集率,酶联免疫吸附试验测定血清P-选择素、血栓素B2表达水平,Western blot检测颈动脉PAR-1蛋白表达,HE染色观察颈总动脉形态学变化,应用计算机图像分析系统测定损伤动脉壁腔比值。结果 1颈动脉球囊损伤后,P-选择素、血栓素B2表达及血小板聚集率均较单纯高脂组增加(P<0.05);而阿托伐他汀治疗显著降低球囊损伤后血清P-选择素、血栓素B2表达,同时抑制了血小板的聚集率(均P<0.05)。2血管球囊损伤后,兔颈动脉PAR-1蛋白的表达较对照组及单纯高脂组增加(高脂+损伤组1.143±0.099比对照组0.172±0.028、单纯高脂组0.184±0.035,P<0.05);阿托伐他汀治疗明显降低了PAR-1蛋白的表达,高剂量他汀组更为明显(低剂量他汀组0.920±0.083、高剂量他汀组0.091±0.013比高脂+损伤组1.143±0.099,均P<0.05)。3高脂喂食后兔颈动脉内膜轻度增生,血管壁腔比值增加;而高脂喂食+球囊损伤后颈动脉新生内膜增殖更明显;5及10mg/(kg·d)的阿托伐他汀治疗抑制了球囊损伤后内膜的增殖,壁腔比值较球囊损伤未治疗组分别下降27%、49%(均P<0.01)。结论强化阿托伐他汀治疗抑制了高脂喂食及血管球囊损伤兔颈动脉PAR-1蛋白的表达,抑制血清P-选择素、血栓素B2表达及血小板聚集,减轻了血管损伤后新生内膜的增殖。Objective To investigate the effects of atorvastatin on the expression of protease-activated receptor（PAR）-1in platelet activation and the changes of neointimal hyperplasia after balloon-induced carotid artery injury in cholesterol-fed rabbits. Methods A total of 30 rabbits were randomly treated as follows：control,fed with cholesterol-enriched diet＋sham-operated（pure high fat group）,fed with cholesterol-enriched diet＋balloon-injured（high fat＋balloon-injured group）,balloon injury and treated with 5mg/（kg·d）atorvastatin（L-atorvastatin group）and10mg/（kg·d）（H-atorvastatin group）,n=6. Platelet aggregation rate was measured by turbidimetric platelet aggregometry. The levels of P-selectin and thromboxane B2 were detected by enzyme-linked immunosorbent assay.After 28 days,wall-to-lumen area ratios（W/L）of the injured arteries were calculated using a computer image analysis system and the protein expression of PAR-1in all rabbits was detected with Western blot. HE staining was used to detect carotid morphological changes. Results ①Compared with the pure high fat group,the level of P-selectin,thromboxane B2 and platelet aggregation was significantly increased and reached a peak at 24 th hour after balloon injury. And treatment with atorvastatin dose-dependently decreased the level of P-selectin and thromboxane B2,as well as,inhibited the platelet aggregation（P〈0.05）.②After high-cholesterol diet and vascular injury,the expression of PAR-1protein significantly increased in comparison with the control group and pure high fat group,whereas it could be markedly decreased by atorvastatin treatment in a dose-dependent manner（pure high fat＋balloon-injured group：1.143±0.099 vs control group：0.172±0.028,pure high fat group：0.184±0.035;L-atorvastatin：0.920±0.083,H-atorvastatin：0.091±0.013 vs pure high fat＋balloon-injured group：1.143±0.099,all P〈0.05）.③Compared with control group,the W/L of pure high fat group and pure high fat＋balloon-injured group wer

关 键 词：阿托伐他汀 血管球囊损伤 蛋白酶活化受体1 血小板聚集 内膜增殖 

分 类 号：R543.4[医药卫生—心血管疾病]