单核细胞趋化蛋白1反义寡核苷酸抑制大鼠腹主动脉瘤的形成

The Effect of Antisense Oligodeoxynucleotides of Monocyte Chemoattractant Protein-1 on the Formation of Abdominal Aortic Aneurysm in Rats

为了观察单核细胞趋化蛋白 1对腹主动脉瘤形成的影响 ,建立大鼠腹主动脉瘤模型 ,局部转染单核细胞趋化蛋白 1基因的反义寡核苷酸。结果表明 :动脉灌注 3d ,苏木素—伊红染色即可见明显的炎性细胞浸润 ,逆转录聚合酶链反应提示单核细胞趋化蛋白 1的mRNA表达在灌注 14d达高峰 ,蛋白印迹及免疫组织化学染色提示蛋白产物均在 14d达到高峰 ,并且与动脉瘤的形成呈平行关系。反义寡核苷酸可以抑制单核细胞趋化蛋白 1基因的mRNA及蛋白产物表达 (P <0 .0 1) ,延缓腹主动脉瘤形成 ,抑制率为 92 %～ 12 5 % ,并存在一定的量效关系。本研究提示单核细胞趋化蛋白 1参与腹主动脉瘤的形成 ,反义技术可以减少单核巨噬细胞浸润并抑制腹主动脉瘤的形成和发展。

Aim To investigate the effect of monocyte chemoattractant protein (MCP)-1 on the formation of abdominal aorta aneurysm (AAA). Methods AAA model was established by perfusion of pancreas elasticity proteinase in 66 rats, which were divided into control team, Oligodeoxynucleotides (ODNs) team and Lipofectin team. ODNs teams were treated by local application of ODNs, antisense ODNs or scramble ODNs in dosage of 50 μg or 100 μg. Lipofectin and pluronic gel were used. The specimen were havested on 14 d after operation. Results Prominantly infiltration of inflammtory cell was evident in aortic tissue 3 d after operation. MCP-1mRNA was dectected by RT-PCR which increased and reached the peak on 14 d after operation. The expression of MCP-1 and CD68 were measured by immunohistochemistry and Western blotting, and reached the peak on 14 d after surgery. Antisense ODNs could inhibit the expression of MCP-1 mRNA prominantly. Antisense ODNs could prevent AAA formation and had a dosage dependent relationship. Conclusions MCP-1 took part in the formation of AAA. Inhibiting the expression of MCP-1mRNA by antisense technology could reduce the infiltration of macrophage and AAA formation.