载脂蛋白E基因敲除小鼠动脉粥样硬化早期血管外膜血管细胞黏附分子1和细胞间黏附分子1的表达

Expression of Vascular Adventitial VCAM-1 and ICAM-1 at the Early Stage of Atherosclerosis in Apolipoprotein E Knockout Mice

目的探讨血管外膜血管细胞黏附分子1和细胞间黏附分子1在动脉粥样硬化病灶形成及发展中的作用。方法 6周龄载脂蛋白E基因敲除小鼠和野生型C57BL/6小鼠,高脂饮食喂养2、4和8周,选取升主动脉制备连续切片,部分切片行Movat染色,观察组织形态学变化并测量外膜厚度的变化;部分切片用免疫组织化学法观察不同阶段血管外膜及内膜血管细胞黏附分子1和细胞间黏附分子1表达的动态变化。结果 6周龄载脂蛋白E基因敲除小鼠和各个时间点的C57BL/6小鼠均未观察到内膜损伤的任何迹象,主动脉外膜厚度亦无显著变化,外膜均无血管细胞黏附分子1的表达;高脂喂养2周后,载脂蛋白E基因敲除小鼠血管外膜厚度增加,但在内膜仍无肉眼可见病灶,此时外膜血管细胞黏附分子1呈现弱阳性表达;高脂喂养4周和8周后,载脂蛋白E基因敲除小鼠血管外膜厚度逐渐增加,内膜出现泡沫细胞,纤维斑块,外膜及内膜损伤处血管细胞黏附分子1表达增强。载脂蛋白E基因敲除小鼠随着高脂喂养时间延长,主动脉外膜及内膜细胞间黏附分子1的表达也增加,但C57BL/6小鼠血管外膜细胞间黏附分子1表达量少且稳定,各时间点之间无明显差异。结论载脂蛋白E基因敲除小鼠随着高脂喂养时间延长血管外膜血管细胞黏附分子1和细胞间黏附分子1的表达增加。

Aim To study the effects of vascular adventitial vascular cell adhesion molecule-1（VCAM-1） and intercellular adhesion molecule-1（ICAM-1） on atherosclerotic lesion formation. Methods Apolipoprotein E Knockout（ApoE-/-） mice and wild-type C57BL/6 black mice of 6 weeks were used in this experiment.All animals were fed hyperlipidic diet for 2,4 and 8 weeks.The ascending aorta was removed with the heart attached for serial sectioning.Some sections were stained by Movat method in order to observe the morphological changes of the tissues and measure the thickness of vascular adventitia.Some sections were stained with immunohistochemistry to observe the changes in the expression of vascular adventitial ICAM-1 and VCAM-1 at different stages. Results ApoE-/-mice of 6 weeks and C57BL/6 mice at any time point did not show any changes of adventitial thickness,nor expression of VCAM-1,nor intimal lesion formation.After hyperlipidic diet for 2 weeks in ApoE-/-mice,the adventitial thickness increased and the expression of VCAM-1 was found in the adventitia when there was no visible intimal lesion formation.After hyperlipidic diet for 4 weeks the foam cells were showed in the intima and the atherosclerotic lesion developed after hyperlipidic diet for 8 weeks in ApoE-/-mice.The adventitial thickness and the expression of VCAM-1 in adventitia and intimal lesion of ApoE-/-mice increased.The expression of ICAM-1 in the adventitia and the intima of ApoE-/-mice increased gradually with increasing duration of the hyperlipidic diet.However the expression of ICAM-1 was infrequent and stable in C57BL/6 mice. Conclusion The expression of VCAM-1 and ICAM-1 in the adventitia of ApoE-/-mice increased gradually with increasing duration of the hyperlipidic diet.