复方花刺参黏多糖对血管损伤后再狭窄家兔血管内膜增殖与凋亡的影响

摘要

目的 探讨复方花刺参黏多糖对家兔髂动脉腔内血管成形术(TA)后内皮功能及内膜增殖与凋亡的影响.方法 50只新西兰纯种家兔随机分为4组:花刺参组、辛伐他汀组、模型组和正常对照组.各组动物于TA后4周空腹颈动脉同步采血行MDA、ET、NO含量及vWF、SOD活性测定,并全部处死动物行病理形态学检查、原位杂交染色观测血小板衍生生长因子(PDGF)、成纤维细胞生长因子(bFGF)、转化生长因子-β1(TGF-111) mRNA在髂动脉中的表达及末端标记法检测凋亡细胞.结果 (1)TA后4周,模型组血浆中MDA、ET含量及vWF活性明显高于正常对照组(P＜0.01),而血清NO含量及SOD活性则显著低于正常对照组(P＜0.01)；辛伐他汀组MDA、ET含量及vWF活性均明显低于模型组(P＜0.01),NO含量及SOD活性则显著高于模型组(P＜0.01).(2)模型组内膜厚度明显高于花刺参组和辛伐他汀组(P＜0.01)；模型组管腔狭窄度明显高于花刺参组和辛伐他汀组(P＜0.01).(3)正常对照组PDGF仅内膜微量表达；模型组内膜强烈表达,中膜中度表达,较正常对照组明显增多(P＜0.01)；花刺参组及辛伐他汀组PDGF表达局限于内膜,伴或不伴中膜轻微表达,与模型组比较明显减少(P＜0.05).模型组内膜及中膜TGF-β1强烈表达,比正常组明显增多(P＜0.01)；花刺参组及辛伐他汀组TGF-111表达比模型组明显减少(P＜0.05).(4)免疫组化显示花刺参组、辛伐他汀组和模型组较正常对照组平滑肌细胞凋亡率明显增加,模型组较花刺参组和辛伐他汀组平滑肌细胞凋亡更加显著(P＜0.05).结论 复方花刺参黏多糖具有抑制家兔血管成形术后内膜增殖和保护内皮功能的作用.%Objective To investigate the effect of stichopus variegates compound on the iliac arterial endothelial function and neointimal proliferation and apoptosis after transluminal balloon angioplasty (TA) of iliac atherosclerosis model with rabbits. Methods Fifty purebred New Zealand rabbits were randomly divided into four groups: stichopus group, simvastatin group, model group and normal control group. After four weeks since transluminal balloon angioplasty, the blood was collected from left carotid artery to measure the changes of concentrations of model driven architecture (MDA) , endothelin (ET) , nitric oxide (NO) , von Willebrand Factor (vWF) and super oxide dlsmutase (SOD). After 4 weeks, pathological morphology was inspected, in situ hybridization dyeing observation platelet derived growth factor (PDGF) , fibroblast growth factor (bFGF) , transforming growth factor-β1 (TGF-β1 ) mRNA expression and in iliac artery end labeling method to detect the apoptotic cells. Results (1) After four weeks since TA, the concentrations of plasm MDA, ET and vWF in model groups increased significantly comparing with the normal control groups ( P <0. 01 ) ; and the concentrations of serum NO and SOD decreased significantly ( P <0. 01) ; the concentrations of plasm MDA, ET and vWF in model groups were higher than those in the simvastatin groups and stichopus groups ( P < 0. 01) ; and the concentrations of serum NO and SOD decreased obviously ( P < 0. 01) . (2) After four weeks since TA, neointimal mean thickness of segment operated transluminal angioplasty in model groups increased significantly, comparing with simvastatin groups and stichopus groups ( P <0.01) ; There were less luminal areas in model groups than those in simvastatin groups and stichopus groups ( P <0. 01) ; there were no significant difference in areas under internal elasticity membrane of three groups. There were greater extent of lumen stenosis in model groups than those in simvastatin groups and stichopus groups ( P <0. 01). (3) Normal endometrium PDGF only trace expression, model group endome-trial strong expression than normal group moderate significantly increased ( P <0.01) , stichopus group and simvastatin group PDGF express confined to lining, with or without an accompanying slightly in expression, and model membrane group compared significantly reduced ( P <0. 05). Model group lining and membrane TGF-β1 strong expression, than the normal control group were significantly increased ( P <0.01) ; Stichopus group and simvastatin TGF-β1 expression of than model group significantly reduced ( P <0.05). (4) Immunohistochemical displayed that the stichopus group, simvastatin group and the model group had more normal smooth muscle cell apoptosis rate of increased significantly, the model group, stichopus group and simvastatin group of smooth muscle cell apoptosis more significant ( P < 0. 05). Conclusion It demonstated that the stichopus variegatus compound could significantly inhibit the vessel smooth muscle cells proliferation, and protect the endothe-lial function after iliac arterial transluminal angioplasty of rabbits.