目的:研究稳定斑块组织因子(TF)活化表达及在血栓形成中的作用。方法:建立ApoE-/-小鼠动脉粥样硬化病变的动物模型,一期凝固法检测小鼠血浆TF特异性的促凝活性,光镜和电镜观察稳定斑块病变,免疫组化SP法检测小鼠稳定斑块TF的蛋白表达,原位杂交法检测小鼠稳定斑块TFmRNA表达。结果:ApoE-/-小鼠血浆促凝活性显著增加(P〈0.01),并随着诱发斑块时间的延长呈上升趋势,抗TF单抗能显著抑制血浆促凝活性(P〈0.01);实验小鼠的病变为稳定斑块,电镜下,ApoE-/-小鼠可见完整的血管内皮细胞,在内皮完整的血管内有血小板的聚集;不同狭窄程度的ApoE-/-小鼠动脉粥样硬化病变部位TF的表达差异有统计学意义(P〈0.01),TF的表达随着粥样硬化病变的进展而增强,TFmRNA与TF蛋白表达一致。结论:TF可能通过活化和释放启动凝血过程,导致血栓的形成;TF不仅是粥样硬化导致动脉损伤的结果,还可能是促进动脉粥样硬化病变的重要原因。
Objective:To study expression and activity of tissue factor in atherosclerosis stable plaque of ApoE -/- mice. Method..ApoE-/- mice were raised to induce the atherosclerosis stable plaque in 29 weeks. Procoagulant activity of tissue factor in ApoE-/- mice plasma was measured in 12,16,20,24,28 weeks. Pathological changes of the plaque were observed under microscope. Expression of tissue factor mRNA and protein were examined in aorta by using in situ hybridization and immunohistoehemistry. Result: Procoagulant activity of tissue factor in ApoE-/- mice plasma was significant higher than that in control group(P〈0.01), and raised by the course of experiment. It can be significant inhibited by tissue factor antibody(P〈0.01). Most of the ApoE-/- mice got the stable pique successfully. Under electron microscope, we observed intact vascular endothelial cell in ApoE-/- mice aorta, but with platelets aggregation. Expression of tissue factor protein and mRNA in atherosclerosis stable plaque was significantly different in ApoE-/- mice(P〈0.01). Tissue factor enhanced by the progress of atherosclerosis. Conclusion:Tissue factor may start blood clotting to induced thrombosis by activation and releasing. Tissue factor is not only the result of the vascular injury by atherosclerosis, but also the reason of atherosclerosis.