Toll样受体4及NF-κB与动脉粥样硬化关系的实验研究

Experimental study of relationship between Toll-like receptor 4,NF-κB and atherosclerosis in rabbits

目的 观察球囊损伤后动脉粥样硬化兔颈动脉干Toll样受体4（TLR4）、NF-κB及其表达变化.方法 本实验首先通过球囊损伤颈总动脉的方法在高脂饲养的兔子体内引起一个持续性的低水平的局部炎性介质反应,建立双因素干预的动物粥样硬化模型,以促进兔颈总动脉的血管病变,同时将全部动物分为对照组、高脂饲养组和模型（双因素）组,8周后处死动物留取组织标本,观察HE染色的兔颈总动脉形态学变化,检测动脉壁TLR4和NF-κB的表达.结果 高脂饲养组和模型组血管内皮细胞TLR4和NF-κB表达水平均较对照组增高（P＜0.01）,且模型组升高的程度明显高于高脂饲养组（P＜O.01）.结论 高脂血症、慢性炎性介质反应均可能是通过TLR4/NF-κB信号途径促进动脉血管病理学改变;证实了炎性刺激能加快动脉粥样硬化的进程;TLR4/NF-κB信号途径在体内环境的变化与动脉形态学变化之间起到了桥梁作用.

Objective To observe the role of chronic inflammation in the development of atherosclerosis （AS） by analyzing the expression of TLR4 and NF-κB in artery endothelium. Methods To construct the atherosclerotic animal model, the balloon catheter was used to injure common carotid artery and rabbits were fed the high cholesterol diet. All the rabbits were divided into three groups： control group with the normal diet, high cholesterol diet-fed group and model group （balloon-injured common carotid artery and the high cholesterol diet fed rabbits）. The rabbits were sacrificed after 8 weeks and their tissues were collected. Then morphological changes of rabbit common carotid artery were observed by light microscope. The expression of TLR4 and NF-κB in endarterium was displayed using immunochemistry method. Results Both hyperlipidemia and exterior inflammatory stimulation promoted the expression of TLR4 and NF-κB in vascular endothelium （P 〈 0.01 ）. And when both of them were present, the level of TLR4 and NF-κB expression would get higher even than that affected by one of them（ P 〈 0.01 ）. Conclusion Both hyperlipidemia and chronic inflammatory process can improve the expression of TLR4 and NF- κB in vascular endothelium in different degree; the inflammatory stimulation would promote the atherosclerosis to some extent; TLR4/ NF-κB would play a role as a bridge between the internal environment changes and the arterial morphological changes.