外膜炎症及炎症因子与大鼠移植物动脉硬化早期发病关系  

Study of adventitial inflammation and inflammatory factors in pathogenesis of allograft arteriosclerosis in rats

作　　者：孙文宇[1] 陆现硕[1] 毕研文[1] 吴树明[1] 

机构地区：[1]山东大学齐鲁医院心外科,济南250012

出　　处：《中华医学杂志》2009年第35期2504-2508,共5页National Medical Journal of China

基　　金：山东省卫生厅科研基金（HZ079）

摘　　要：目的探讨外膜炎症及血清炎症因子与移植物动脉硬化早期发病的关系。方法把36只同种异体胸主动脉腹腔移植大鼠及16只同系移植对照大鼠随机分成4组（每组实验组9只，对照组4只）：A组，术后1周处死；B组，术后2周处死；C组，术后3周处死；D组，术后4周处死。术前及处死时抽血分离留取血清，使用酶联免疫吸附法检测血清炎症因子白细胞介素6（interleukin-6，IL-6）和肿瘤坏死因子α（tumor necrosis factor—alpha，TNF-α）水平，处死后留取血管标本，HE染色观察血管外膜炎症细胞浸润程度及病理改变；用免疫组织化学法检测α-肌动蛋白（α—actin）、周期蛋白依赖性激酶1（eyclin dependent kinase-1，CDK1）、增殖细胞核抗原（proliferating cell nuclear antigen，PCNA）在血管壁中的表达。对比各组与术前血清炎症因子水平变化及各组间观察指标的变化。结果术后7d，外膜大量炎症细胞浸润；术后14d，外膜有轻度胶原纤维增生伴炎症浸润；术后28d，外膜明显增厚，内有大量增生的平滑肌细胞、胶原纤维及炎症细胞，血管中层断裂，可见外膜平滑肌细胞迁移至内膜，内膜亦出现明显纤维化及平滑肌细胞增生。在血管外膜平滑肌细胞中，α-肌动蛋白、PCNA和CDK．表达愈来愈高（均P〈0．05），且早于内膜。移植术后A、B、C、D组血清炎症介质水平均高于术前基础水平。IL-6水平，B实验组高于术前（P〈0．05），A、C、D实验组显著高于术前（均P〈0．01），A、B、C对照组也高于术前基础水平（均P〈0．05）；A、C、D实验组显著高于对照组（均P〈0．01）。TNF—α水平，A、B、C实验组高于术前（均P〈0．05），D实验组显著高于术前（P〈0．01），A、B、C、D对照组与术前无明显变化，各实验组均明显高于对照组（均P〈0．01），差异有统计学意义。结论大鼠同种异体胸主动脉移�Objective To study the roles of serum inflammatory factors IL-6 and TNF-α and allograft adventitial inflammation in the pathogenesis of allograft arteriosclerosis in rats. Methods Thirty-six allogeneic allograft rats and 16 syngeneic allograft rats were randomly divided into 4 groups （9 rats in each experimental group and 4 in each control group） ： A, harvested at Week 1 post-operation; B, harvested at Week 2 post-operation; C, harvested at Week 3 post-operation; D, harvested at Week 4 post-operation. Blood samples were collected before transplantation and after harvest. The method of ELISA was used for testing serum inflammatory factors including interleukin-6 （ IL-6 ）, tumor necrosis factor-α （TNF-α） , HE staining for pathologic changes of aortic allograft and immunohistochemical method for expression of α-actin, cyclin dependent kinase-1 （CDK1） and proliferating cell nuclear antigen （PCNA）. Compare the inflammatory factors and other observations between groups and preoperative. Results At Week 1 postoperation, a large amount of inflammatory cell infiltration in adventitia was observed; at Week 2 postoperation, slight collagen fibers hyperplasia with inflammatory infiltration; at Week 4 post-operation, obvious adventitia thickening with a large number of smooth muscle cells, collagen fibers and inflammatory cells, smooth muscle cells migration from adventitia to intima. Expressions of α-actin, CDK1 and PCNA kept increasing with time in adventitia （ P 〈 0. 05 ）. There was a significant increase in serum TNF-α level in Groups A, B, C and D, as compared with pre-operative basal level （P 〈 0. 01 ）. There was no difference between controls and pre-operative basal level. IL-6 level slightly declined in the middle stage, but finally increased in experimental group B （ P 〈 0. 05 ） while it significantly increased in Groups A, C, D （ P 〈 0. 01 ）. In the control groups A, B, C, it was higher than pre-operative level （P 〈 0. 05）. In experimental groups A, C, D, it

关 键 词：移植物 动脉硬化 炎症 

分 类 号：R686[医药卫生—骨科学]