CAJ | 학술논문

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60 d；(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60 d;(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60 d.术后60 d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)；异系移植实验蛆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(P＜0.05)；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VEGF表达下调和内皮细胞结构功能改变相关.
목적 탐토사리도알대대서이식동맥만성이식물혈관병적개선작용급기궤제.방법 이Brown-Norway대서화Lewis대서제비대서복주동맥만성이식물혈관병모형,모형분위3조:(1)동계이식대조조,공、수서균위Brown-Norway대서,술후매천이생리염수관위지술후60 d；(2)이계이식대조조,이Brown-Norway대서위공서,Lewis대서위수서,수서술후매천이생리염수관위지술후60 d;(3)이계이식실험조,이Brown-Norway대서위공서,Lewis대서위수서,수서술후이사리도알100mg·kg-1·d-1관위60 d.술후60 d절취이식혈관분별재광경하관찰이식물혈관조직형태학적변화,재전자현미경하관찰혈관내피세포급중막평활기초미결구적변화；채용면역조직화학법측정이식동맥조직중혈관내피세포생장인자(VEGF)적표체.결과 광경하,이계이식대조조화이계이식실험조혈관내막증생정도초과동계이식대조조(P＜0.05)；이계이식실험저내막증생정도교이계이식대조조경(P＜0.05).투사전경하,여동계이식대조조상비교,이계이식대조조화이계이식실험조내피세포변성배사,평활기세포고축명현,중성립세포공포변성정도중；이계이식실험조내피세포、평활기세포변성배사정도교이계이식대조조경.동계이식대조조이식동맥중VEGF양세포수위(1.218±0.118)개,저우이계이식대조조적(32.124±2.003)개화이계이식실험조적(10.873±1.932)개(P＜0.05)；이계이식실험조VEGF양세포수저우이계이식대조조(P＜0.05).결론 사리도알구유완해만성이식물혈관병적작용,궤제가능여VEGF표체하조화내피세포결구공능개변상관.
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 factor (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.