兔颈总动脉破裂粥样硬化斑块模型的建立

Establishment of model of carotid atherosclerosis plaque rupture in rabbits

目的建立负压吸引激发兔颈总动脉粥样硬化斑块破裂,建立破裂斑块模型。方法将30只健康雄性新西兰白兔随机分为3组,分别为对照组(n=10)、高脂饲养组(n=10)和球囊损伤+高脂饲养组(n=10)。饲养8周后,彩色多普勒超声测量颈总动脉内径、内-中膜厚度(IMT)及颈动脉血流速度等,评估动脉IMT与动脉粥样硬化程度的关系。采用"腔外负压"法诱导斑块破裂并处死动物,观察诱发斑块破裂成功率,在肉眼及光镜下观察颈动脉内膜形态特征。结果球囊损伤+高脂饲养组、高脂饲养组的颈总动脉血流速度显著快于对照组,IMT显著厚于对照组,颈总动脉内径显著短于对照组;球囊损伤+高脂饲养组的颈总动脉内径显著短于高脂饲养组,IMT显著厚于高脂饲养组,颈总动脉血流速度显著快于高脂饲养组(P<0.05)。球囊损伤+高脂饲养组可见平滑肌细胞增生,脂质、炎症细胞、泡沫细胞浸润,符合不稳定性斑块特征,有8例诱发斑块破裂,1例死亡;高脂饲养组可见内膜下脂质沉积,炎症细胞浸润,但内皮细胞完整,内弹力板排列整齐,1例诱发斑块破裂,无动物死亡;对照组内皮细胞完整,中层平滑肌细胞排列整齐,无一例诱发斑块破裂,无动物死亡。结论本实验建立动脉粥样硬化斑块破裂模型成功率高,动物死亡率低,实验操作简便易行,为冠心病的生理、病理及药物学效应方面研究提供了可靠的实验平台。

Objective To establish an animal model of plaque rupture by negative barometric pressure triggering carotid atherosclerosis plaque.Methods 30 healthy New Zealand white male rabbits were randomly divided into 3 groups,including control group（n=10）,high fat-diet group（n=10）and carotid lesion with balloon dilation and high fat-diet group （n=10）.After 8 weeks,carotid artery diameterthe,intima-media thickness （IMT）and blood flow rate of carotids was measured respectively by color Doppler ultrasound,the relationship between IMT and the severity of atherosclerosis was evaluated.Plaque ruptures were triggered by negative pressures of extra-cavity,all rabbits were sacrificed.The success rate of plaque rupturethe was observed and carotid intima morphology was observed in the naked eye and the light mi- croscope.Results Carotid artery blood flow velocity in high fat-diet group and carotid lesion with balloon dilation and high fat-diet group was significantly faster than that in control group respectively,IMT in high fat-diet group and carotid lesion with balloon dilation and high fat-diet group was significantly thicker than that in control group respec- tively,carotid artery diametertbe in high fat-diet group and carotid lesion with balloon dilation and high fat-diet group was significantly shorter than that in control group respectively（P〈0.05）.Carotid artery blood flow velocity in carotid le- sion with balloon dilation and high fat-diet group was significantly faster than that in high fat-diet group,IMT in carotid lesion with balloon dilation and high fat-diet group was significantly thicker than that in high fat-diet group,carotid artery diameterthe in carotid lesion with balloon dilation and high fat-diet group was significantly shorter than that in high fat-diet group （P〈0.05）.The typical pathological changes of atherosclerosis,such as thickening of the carotid endomembrane,transmigration and proliferation of smooth muscle cells,lipidosis,inflammatory cell and foam cells infiltration,carotid arteries inner elastic force layer frac- ture,formations of atherosclerosis plaque were found in rabbits of carotid lesion with balloon dilation and high fat-diet group,and 8 rabbits were triggered by negative barometric pressure,only one rabbit dead.Deposition of lipid membrane,inflammatory cell infiltration,but the endothelial cells,internal elastic plate arranged in neat rows were seen in the high fat-diet group, l case nf induced plaque nlpture, no animal death.Endothelial cell integrity,smooth muscle cells arranged in neat rows in conlrol group, l vase withoul in- ducing plaque rupture,no animal death.Conclusion This study has been established a new ,nethod of atherosclerosis and plaque rupture of carotid atberosclerotic in rabbit of which would be setting a reliable research platform of coronarv heart disease such as physiology,pathology and effects of drug.