摘要
目的:研究在体脉动低切应力致实验兔颈总动脉粥样硬化(AS)的炎性反应机制。方法:结扎成年雄性新西兰白兔(体质量2.5～3.0kg)的左颈外动脉获得左颈总动脉脉动低切应力;然后用高脂(含2%胆固醇)或普通饲料(100g/d)养兔至2、4、8、12周,取下两侧颈总动脉;用原位杂交技术检测C反应蛋白(CRP)mRNA和单核趋化蛋白1(MCP1)mRNA,免疫组化方法检测NF-κB、IL-1β、ICAM-1、VCAM-1、PDGF-A、B等蛋白的表达。结果:建立了两类脉动低切应力AS模型;不论是否喂高脂饲料,脉动低切应力侧(左)颈总动脉均有AS斑块形成,其炎症标志因子CRP、MCP-1、NF-κB、IL-1β、ICAM-1、VCAM-1、PDGF-A、B等的mRNA和蛋白表达比假手术正常切应力对照侧(右颈总动脉)均明显增高。结论:从组织、细胞、分子多个层次和炎症反应多个环节证明了脉动低切应力致AS的炎症机制。为用生物医学工程方法和抗炎药物防治AS提供了依据。
Objective:To analyze the inflammatory mechanism of pulsatile low shear stress-induced atherosclerosis (AS) of the common carotid artery in rabbits in vivo. Methods: The left external carotid arteries of 40 adult New Zealand white rabbits were ligated to develop pulsatile low shear stress in the left common carotid,and then the rabbits were fed on a specially formulated hyperlipotic (2% cholesterol) or a standard chow for 2,4,8 and 12 weeks. Two common carotid arteries of each rabbit were harvested. The inflammatory factors CRP mRNA and MCP-1 mRNA were detected by in situ hybridization,and NF-κB,IL-1β,ICAM-1,VCAM-1 and PDGF-A,B were detected by immunohistochemistry staining. Results: Two types of pulsatile low shear stress-AS models were established. Atherosclerotic plaques were found in the left common carotid arteries regardless of food ingestion. The inflammatory factors were all up-regulated in the pulsatile-low-shear-stress left (not normal-shear-stress right) common carotid arteries. Conclusion: The pulsatile low shear stress-induced inflammatory mechanism of AS is elucidated from the molecular,cellular and histological aspects,providing a foundation for AS prevention and treatment by biomedical engineering method and anti-inflammatory drugs.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
2005年第6期642-647,共6页
Academic Journal of Second Military Medical University
关键词
动脉硬化
颈总动脉
脉动低切应力
炎症趋化因子类
arteriosclerosis
carotid artery,common
pulsatile low shear stress
chemokines
