兔动脉粥样硬化易损斑块早期预警指标的回归性研究

Predictors of vulnerable atherosclerotic plaques induced by cholesterol and balloon injury in rabbits

目的 通过对动脉粥样硬化易损斑块破裂前各项检测指标的回归分析,明确预测易损斑块破裂的最佳指标.方法 40只雄性新西兰纯种兔用球囊损伤腹主动脉＋高脂喂养10周,于8周末分为p53基因组（20只）和LacZ基因组（20只）,在腹主动脉斑块形成处分别转染携带人野生型p53基因或LacZ基因的重组腺病毒载体,2周后分别给予中国斑点蝰蛇毒（CRVV）和组胺药物触发斑块破裂.应用酶联免疫吸附法（ELISA）检测斑块破裂前血清中的高敏C反应蛋白（hs-CRP）、可溶性细胞间黏附分子-1（sICAM-1）和可溶性血管细胞间黏附分子（sVCAM-1）的变化,免疫比浊法测定血浆中纤维蛋白原的水平,联合应用体表超声心动图、血管内超声（IVUS）显像仪和声学密度定量（AD）技术检测易损斑块破裂前的各项影像学指标及声学密度强度,利用logistic回归分析判断以上各项检测指标与易损斑块破裂的关系.结果两组实验兔在药物触发后有21只兔共34处发生斑块破裂及血栓形成.p53基因组（存活19只）斑块破裂率89.5%（17/19）,与LacZ基因组（存活18只）斑块破裂率22.2%（4/18）比较,差异有统计学意义（P＜0.01）.药物触发前,斑块破裂组（n=21）hs-CRP水平、体表血管超声测值（腹主动脉内膜中层厚度、峰值速度）、AD值、IVUS测值明显高于斑块未破裂组（n=16）,logistic回归分析显示IVUS测值斑块偏心指数（EI）、斑块面积（PA）和血清学sVCAM-1的OR值分别为26.917、19.301和1.339（均P＜0.05）,校正的AD值AⅡ-c%的OR值为0.458（P＜0.05）.结论 IVUS测值E1、PA、血清学指标sVCAM-1以及AD值是预测斑块易损性的重要指标.

Objective To detect the optimal predictors of vulnerable atherosclerotic plaques. Methods Forty New Zealand white rabbits underwent balloon-induced abdominal aortic wall injury and were fed a high cholesterol and saturated fat diet containing 1% cholesterol for 8 weeks. Rabbits were then randomly divided into two groups： group A （ n = 20, the aortic segments rich in plaques were incubated transluminally with recombinant adenovirus carrying p53 ） and group B [n = 20, incubated transluminally with β galactosidase （LacZ） genes]. Two weeks later, rabbits underwent pharmacological triggering with injection of Chinese Russell＇s viper venom （CRVV） and histamine. Before pharmacologically triggering,concentrations of hs-CRP, sVCAM-1 and sICAM-1 were measured by means of Enzyme-linkedimmunosorbent assay （ELISA）. Fibrinogen was analyzed by nephelometer. Ultrasound imaging, accuracy densitometry （AD） examination and intravascular ultrasound （IVUS） were performed to analyze the in vivo features of vulnerable plaques. Logistic regression was used to detect the predictors for vulnerable plaques. Results The ratio d plaque rupture after pharmacological triggering was significantly higher in group A （89.5% ,17/19） than in group B （22.2%,4/18）. Serum hs-CRP level was significantly higher in plaque rupture group than in non-rupture group before pharmacological triggering （P 〈 0. 05 ）. In the meantime, parameters derived from ultrasound imaging [intima-media thickness （IMT） and peak velocity （VP）, values of accuracy densitometry], measurements of IVUS [external elastic membrance area （EEMA）,plaque area（PA）, plaque burden （PB）, eccentric index （EI） and remodeling index（RI）]were significantly larger in plaque rupture group than in non-rupture group. Logistic regression showed that EI（OR=26.917）,PA（OR=19.301）, sVCAM-1（OR=1.339）and AⅡ-c%（OR=0.458）were independent predictors for plaque rupture（all P〈0.05）.Conclusion The major predictors of vulnerable plaques were eccentric index （EI） and plaque area（PA）, sVCAM-1 and AⅡ-c% in this model.