Sun Wen-yu, Lu Xian-shuo, Bi Yan-wen, Wu Shu-ming
Department of Cardiac Surgery, Qilu Hospital, Shandong University, Jinan, China.
Zhonghua Yi Xue Za Zhi. 2009 Sep 22;89(35):2504-8.
To study the roles of serum inflammatory factors IL-6 and TNF-alpha and allograft adventitial inflammation in the pathogenesis of allograft arteriosclerosis in rats.
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-alpha(TNF-alpha), HE staining for pathologic changes of aortic allograft and immunohistochemical method for expression of alpha-actin, cyclin dependent kinase-1 (CDK(1)) and proliferating cell nuclear antigen (PCNA). Compare the inflammatory factors and other observations between groups and preoperative.
At Week 1 post-operation, a large amount of inflammatory cell infiltration in adventitia was observed; at Week 2 post-operation, 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 alpha-actin, CDK(1) and PCNA kept increasing with time in adventitia (P < 0.05). There was a significant increase in serum TNF-alpha 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 had a significant increase as compared with controls (P < 0.01).
In abdominal aortic allograft models, obvious angiosclerosis was found in adventitia and intima in accordance with the severity of adventitial inflammation. Thus the inflammatory factors and inflammatory cell infiltration in adventitia are both involved in the pathogenesis of early allograft arteriosclerosis.
研究血清炎症因子白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）以及同种异体移植物外膜炎症在大鼠同种异体移植动脉硬化发病机制中的作用。
将36只同种异体移植大鼠和16只同基因移植大鼠随机分为4组（每组实验组9只，每组对照组4只）：A组，术后1周取材；B组，术后2周取材；C组，术后3周取材；D组，术后4周取材。在移植前和取材后采集血样。采用酶联免疫吸附测定（ELISA）法检测血清炎症因子，包括白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α），采用苏木精-伊红（HE）染色观察主动脉同种异体移植物的病理变化，采用免疫组织化学方法检测α-肌动蛋白、细胞周期蛋白依赖性激酶-1（CDK(1)）和增殖细胞核抗原（PCNA）的表达。比较各组之间以及与术前的炎症因子及其他观察指标。
术后1周，外膜可见大量炎性细胞浸润；术后2周，有轻微胶原纤维增生伴炎性浸润；术后4周，外膜明显增厚，有大量平滑肌细胞、胶原纤维和炎性细胞，平滑肌细胞从外膜迁移至内膜。外膜中α-肌动蛋白、CDK(1)和PCNA的表达随时间持续增加（P<0.05）。与术前基础水平相比，A、B、C、D组血清TNF-α水平显著升高（P<0.01）。对照组与术前基础水平无差异。IL-6水平在中期略有下降，但在实验组B中最终升高（P<0.05），而在A、C、D组中显著升高（P<0.01）。在对照组A、B、C中，其高于术前水平（P<0.05）。在实验组A、C、D中，与对照组相比有显著升高（P<0.01）。
在腹主动脉同种异体移植模型中，外膜和内膜出现明显的血管硬化，与外膜炎症的严重程度一致。因此，外膜中的炎症因子和炎性细胞浸润均参与了早期同种异体移植动脉硬化的发病机制。
