摘要
目的建立豚鼠动脉粥样硬化模型并探讨其形成机制,同时与大鼠进行比较,阐明模型特点及优势。方法应用高脂饲料诱导方法,观察豚鼠和大鼠动脉粥样硬化病变的形成情况。HE染色法分析主动脉内膜-中膜厚度、内膜炎性细胞浸润和内膜表层斑块的形成情况;酶法检测血脂,酶联免疫吸附法测定血清Ox-LDL浓度,实时定量PCR检测肝脏LDL-R mRNA表达的变化,免疫组化检测血管内膜CD36蛋白表达的变化。结果与对照组比较,豚鼠模型组动脉内膜明显增厚,单核细胞、巨噬细胞浸润与聚集增加,大量的泡沫细胞聚集形成斑块,而大鼠模型组未出现类似动脉粥样硬化病理改变。机制研究表明豚鼠较大鼠易于诱发形成动脉粥样硬化原因主要在于豚鼠血清Ox-LDL水平明显升高,肝脏LDL-R mRNA表达下调,动脉内膜CD36蛋白表达明显增强等。结论与大鼠不同,经高脂饲料诱导10周后,豚鼠可形成典型动脉粥样硬化病变,其机制主要在于LDL-C代谢异常。
Objective To establish a model of early atherosclerosis in guinea pig and explore its pathogenetic mechanisms,compared with the modeling in rats,and to clarify the characteristics and advantages of this guinea pig model of atherosclerosis.Methods The differences of early atherosclerosis induced by high lipid diets in guinea pig and rat were investigated.Aortic intima-media thickness,intimal inflammatory cells infiltration and plaque development were observed by pathology with HE staining.Serum lipid levels were measured by enzymatic methods.serum Ox-LDL levels were detected by enzyme-linked immunosorbent assay（ELISA）.The relative expressions of LDL-R mRNA in the liver were detected by realtime PCR.The protein expression of CD36 in the atherosclerotic aortic wall was evaluated by immunohistochemistry.Results Compared with the control,the arterial intima was significantly thickened,the infiltration and aggregation of monocytes and macrophages significantly increased,and plaques consisting of foam cells accumulation developed in guinea pigs of the model groups.But such changes were not observed in the rats.The mechanism analysis showed that in comparison with the control group,serum Ox-LDL concentration increased,hepatic LDL-R mRNA expression significantly decreased and CD36 expression in the aorta was markedly enhanced in guinea pigs of the model groups.Conclusion Our findings indicate that different from that in the rats,typical atherosclerosis can be developed in guinea pigs with high lipid diet for 10 weeks.The mechanism is mainly due to the involvement of abnormal metabolism of LDL-C.
出处
《中国实验动物学报》
CAS
CSCD
2011年第3期237-241,280,281,共7页
Acta Laboratorium Animalis Scientia Sinica
基金
科技部"重大新药创制"科技重大专项-综合性新药研究开发技术大平台-创新药物研究开发技术平台建设(2009ZX09301-003)
关键词
豚鼠
动脉粥样硬化
OX-LDL
LDL-R
CD36
Guinea pig
Rat
High lipid diet
Early atherosclerosis
LDL-R
LDL-C
Ox-LDL
CD36
Mechanism
