沙利度胺减轻大鼠移植动脉慢性移植物血管病的研究  

Role and function change of vascular endothelial cells in chronic graft vasculopathy

作　　者：姚许平 任雨 翁国斌 瞿亚红 楼仲冠 徐小明 谢振华 祁洪刚 张曙伟 高文波 楼江涌 

机构地区：[1]宁波市泌尿肾病医院 鄞州第二医院,315000

出　　处：《中华器官移植杂志》2014年第2期112-116,共5页Chinese Journal of Organ Transplantation

基　　金：宁波市自然科学基金（2010A610073）;宁波市自然科学基金（2009A610143）;宁波市医学科技计划项目（2009A23）

摘　　要：目的探讨沙利度胺对大鼠移植动脉慢性移植物血管病的改善作用及其机制。方法以Brown-Norway大鼠和Lewis大鼠制备大鼠腹主动脉慢性移植物血管病模型，模型分为3组：（1）同系移植对照组，供、受鼠均为Brown-Norway大鼠，术后每天以生理盐水灌胃至术后60d；（2）异系移植对照组，以Brown-Norway大鼠为供鼠，Lewis大鼠为受鼠，受鼠术后每天以生理盐水灌胃至术后60d；（3）异系移植实验组，以Brown-Norway大鼠为供鼠，Lewis大鼠为受鼠，受鼠术后以沙利度胺100mg·kg-1·d-1灌胃60d。术后60d切取移植血管分别在光镜下观察移植物血管组织形态学的变化，在电子显微镜下观察血管内皮细胞及中膜平滑肌超微结构的变化；采用免疫组织化学法测定移植动脉组织中血管内皮细胞生长因子（VEGF）的表达。结果光镜下，异系移植对照组和异系移植实验组血管内膜增生程度超过同系移植对照组（P〈0．05）；异系移植实验组内膜增生程度较异系移植对照组轻（P〈0．05）。透射电镜下，与同系移植对照组相比较，异系移植对照组和异系移植实验组内皮细胞变性坏死，平滑肌细胞固缩明显，中性粒细胞空泡变性程度重；异系移植实验组内皮细胞、平滑肌细胞变性坏死程度较异系移植对照组轻。同系移植对照组移植动脉中VEGF阳细胞数为（1．218±0．118）个，低于异系移植对照组的（32．124±2．003）个和异系移植实验组的（10．873±1．932）个（Pd0．05）；异系移植实验组VEGF阳细胞数低于异系移植对照组（P〈0．05）。结论沙利度胺具有缓解慢性移植物血管病的作用，机制可能与Ⅵ1GF表达下调和内皮细胞结构功能改变相关。Objective To study the role and function change of the vascular endothelial cells in chronic graft disease, and to study the protective effects of thalidomide on the development of allograft vasculopathy and its potential mechanisms. Method Rat abdominal aorta transplantation was performed on male Brown-Norway （BN） rats as donors and male Lewis rats as recipients. The recipients were divided into 3 group： allograft control group （BN-Lewis） and isograft control group （BN-BN） with administration of sodium chloride, and experimental group （BN-Lewis） administered with thalidomide for 60 days postoperatively. All recipients were killed to harvest transplanted aorta at 60th day after transplantation. HE staining was used to observe the histological changes. The vascular endothelial cell growth {actor （VEGF） expression was detected by using immunohistochemical method. Electron microscope was used to observe the ultra-structure of the vascular endothelial cells and the smooth muscles. Result Isograft control group showed no obvious changes in transplanted aorta at 60th day after transplantation, but experimental group and allograft control group showed changes in pathologic morphology and ultra-structure related to the transplant vasculopathy to varying degrees. The pathological changes in experimental group were more severe than those in allograft control group. There was statistically significant difference between allograft control group and experimental group in the ratio of media and intimal thickness, and the number of cells positive for VEGF. Conclusion Thalidomide has protective effects on chronic allograft vasculopathy, which might be associated with the down-regulation of VEGF and the function change of the vascular endothelial cells.

关 键 词：血管内皮细胞生长因子类 移植物排斥 慢性 内皮细胞 大鼠 

分 类 号：R654.3[医药卫生—外科学]