NF-κB激活及MCP-1和MMP-9表达在兔颈总动脉瘤中的作用

目的 探讨核转录因子(NF-κB)的激活及单核细胞趋化蛋白-1(MCP-1)和基质金属蛋白酶-9(MMP-9)的表达及在脑动脉瘤(CA)形成中的作用.方法 新西兰兔24只,雌雄各半,随机分成4组:A组(对照组)、B组(1周组)、C组(2周组)、D组(3周组),每组6只.用弹性蛋白酶(EA)滴注法建立兔右颈总动脉瘤模型,并用CTA和HE染色观察模型动脉瘤的形态及病理变化,同时用免疫组化分析NF-κB、MCP-1和MMP-9蛋白表达,RT-PCR检测其mRNA的表达.结果 (1)1周后实验兔行CTA检查,18只实验兔均发现作用血管段形成明显的梭形或囊性动脉瘤,其中可见血栓形成,并且血管有闭塞现象,正常对照组6只兔未发现动脉瘤样病变.HE染色检查,实验组动脉瘤瘤壁变薄,弹性纤维断裂,最终消失,平滑肌细胞减少萎缩,降解明显,对照组也有少量炎性细胞浸润,但未观察到弹力纤维降解和平滑肌退行性变.(2)对照组免疫组化显示未见NF-κB及MCP-1表达,MMP-9极少量表达,RT-PCR结果显示均见少量表达;实验组NF-κB及MCP-1均于1周时表达达高峰,3周时表达明显降低,MMP-9表达呈逐渐增强趋势.结论 NF-κB的活化可能是脑动脉瘤发生与发展的始动因素之一,MCP-1及MMP-9表达增高在脑动脉瘤发生发展过程中起着重要作用.

Abstract：

Objective To study the effects of nuclear factor Kappa B( NF - κB) , MCP - 1 and MMP -9 at the early phase of cerebral aneurysm(CA). Methods 24 healthy New Zealand rabbits, half female and half male, were randomly divided into 4 groups: group A (control group), group B( 1 week), group C(2 weeks), group D (3 weeks), 6 rabbits per - group. The morphologic change of the right common carotid artery and formation of the aneurysm were detected by CT angiography and HE dyeing. Aneurysm samples were collected, and immunohistochemistry and real - time rolymerase chain reaction ( Real - time PCR)used to detect the expression of the proteinum and mRNA of NF - κB, MCP - 1 and MMP - 9. Results (1) After a week, using CT angiography to detect all the 18 experimental rabbits, all of them have found visible fusiform or cystiform aneurysms where the elastase was dropped, and also found that some vessels were obstructed. Aneurysms have not found in all the control group rabbits. The pathological examination of the experimental aneurysms showed that the wall of aneurysm becoming thinner, the internal elastic layers were disrupted or disappeared and the reduced medial vascular smooth muscle cell becoming atrophy or degradation obviously. Inflammatory cell infiltrate were also observed in the control group, but the internal elastic layers degradation and vascular smooth muscle degeneration were not found. (2) The result of immunohistochemistry and Real - time PCR indicate that NF - kB and MCP - 1 reached the peak at 1 week, and decreased at 3 weeks. MMP -9 was increased gradually. The expression of NF - kB and MCP -1 were not found in control group. Conclusion NF - κB activation may be one of the initiating agents in the development of the cerebral aneurysm. MCP - 1 and MMP - 9 significantly increased in CA that play an important role in the pathogenesis of cerebral aneurysm (CA).