摘要
目的探讨雷帕霉素对大鼠移植心脏血管平滑肌细胞表型及内膜增生的影响。方法建立大鼠腹腔内心脏移植模型。实验分为4组,每组8只,正常心脏组:取未经任何处理的Wistar大鼠心脏作为空白对照;同系移植组:供体、受体均为Wistar大鼠,以标准鼠食喂养。异系移植取Wistar大鼠作供体,SD大鼠作受体,分为以下两组,环孢霉素组:术后给予环孢霉素A10mg/(kg·d),皮下注射;雷帕霉素组:术后用雷帕霉素1.25mg/(kg.d)灌胃。移植60天后取移植心脏进行电镜观察、形态学观察和用免疫组织化学法分析移植心脏冠状血管平滑肌激动蛋白α的表达情况。结果正常心脏组和同系移植组移植心脏未见明显冠状血管狭窄。环孢霉素组管腔狭窄程度最明显,雷帕霉素组血管狭窄程度最轻。正常心脏组和同系移植组血管内膜、心肌细胞及心肌间质均未见血管平滑肌激动蛋白α表达。心脏移植60天后,环孢霉素组移植心脏血管内膜大量血管平滑肌激动蛋白α表达,心肌细胞亦有血管平滑肌激动蛋白α表达。雷帕霉素组移植心脏血管内膜血管平滑肌激动蛋白α表达较少。很少有血管平滑肌激动蛋白α表达于心肌间质。各组之间移植心脏血管内膜组织中血管平滑肌激动蛋白α表达差异有显著性。正常心脏组及同系移植组电镜下血管平滑肌细胞呈收缩表型,环孢霉素组可见血管平滑肌细胞呈合成表型,雷帕霉素组见大部分血管平滑肌细胞呈收缩表型。结论雷帕霉素可以抑制大鼠移植心脏血管病变过程中血管平滑肌细胞表型的变化,减轻新生内膜的增生程度。
Aim To investigate the effect of rapamycin on phenotype of VSMC and intimal hyperplasia in rat cardiac allograft. Methods Heterotopic heart transplantation models were established. The experimental rats were divided into four groups. Normal hearts of wistar rats served as controls. In isograft group,hearts from wistar rats were heterotopically transplanted to wistar rats with no immunosuppressant administraiton. In allograft group,hearts from wistar rats were heterotopically transplanted to SD rats. CyclosporineA group had Cyclosporine A,10 mg/（kg·d）,administration subcutaneously. Rapamycin group had rapamycin,1.25 mg/（kg·d）,administration by oral intubation after cardiac transplantation. All of the animals were killed at 60 day after transplantation. Phenotype of VSMC was observed with electron microscope. Coronary artery were analyzed for intimal area. Immunohistochemistry method was used for analysing the expression of VSM α-actin in the cardiac allograft. Results In normal hearts and isografts,the vascular intimal thickness were lower than those in the allografts. Compared with cyclosporine treated allografts,the vessel disease in Rapamycin treated allografts decreased significantly 60 days after transplantation （P〈0.01）. In normal hearts and isografts,VSMα-actin was only localized in media. Electron microscope showed VSMC were contractile. VSMα-actin was found in the proliferative vascular intimal in Cyclosporine A treated allografts and electron micro scope showed most of VSMC changed from contractile to synthetic. It was abundant in the proliferative vascular intimal 60 days after transplantation in Cyclosporine A treated allografts while decreased in Rapamycin treated allografts and electron microscope showed the morphologic characteristic of VSMC changed from synthetic to contractile. Conclusion Rapamycin can influence the phenotype transform of VSMC,and reduce the degree of neointimal hyperplasia of transplanted cardiac in rat.
出处
《中国动脉硬化杂志》
CAS
CSCD
北大核心
2010年第4期279-282,共4页
Chinese Journal of Arteriosclerosis
关键词
雷帕霉素
大鼠
心脏移植
血管平滑肌细胞
血管平滑肌激动蛋白α
内膜增生
电镜
Rapamycin
Rats
Cardiac Transplantation
Vascular Smooth Muscle Cell
Vascular Smooth Muscle α-actin
Neointimal Proliferation
Electron Microscope
