局部缓释雷公藤内酯醇对移植静脉平滑肌细胞增殖和凋亡的影响

Effects of local applied slow-releasing triptolide on proliferation and apoptosis of VSMCs of the vein graft

目的:研究经外膜缓释雷公藤内酯醇(Triptolide,TL)对自体移植静脉血管平滑肌细胞(Vascular smooth muscle cells,VSMC)增殖和凋亡的影响。方法:健康家兔24只,建立颈外静脉-颈总动脉移植模型,随机分为3组,空白对照组:移植血管不给任何处理;F-127多聚凝胶对照组:在移植血管外膜喷洒含二甲亚砜(DMSO)0.1ml的20%F-127多聚凝胶0.5ml;实验组:在移植血管外膜喷洒携带TL300μg的F-127多聚凝胶0.5ml。术后2周取标本,组织形态学方法检测血管内膜增生程度,免疫组化检测标本中增殖细胞核抗原(PCNA)和bcl-2的表达情况,TUNEL法检测标本中VSMC凋亡的水平。结果:静脉移植2周后,与空白组和F-127对照组比较,局部应用TL300μg明显抑制血管内膜增生(P<0.05),PCNA、bcl-2的表达均显著减少(P<0.05),TUNEL阳性细胞显著增加(P<0.05)。结论:经外膜缓释TL可以抑制移植静脉VSMC增殖和促进VSMC凋亡,从而抑制血管内膜增生。

Objectives：To investigate the effect and mechanism of adventitia applied slow-releasing triptolide on proliferation and apoptosis of VSMCs of the autologous vein graft. Methods：Twenty-four healthy rabbits were made external jugular vein to common carotid artery models and then were divided into 3 equal groups at random：Blank-control group received no management on adventitia of the vein graft;F-127 pluronic gel control group received local application of 0.5 ml 20% F-127 pluronic gel containing O.lml DMSO on adventitia;and experimental group received local application of 0.5 ml F-127 pluronic gel containing triptolide 300μg on adventitia. Vein graft samples were harvested at 2 weeks after the operation. Histomorphologic methods were used to detect the degree of intima hyperplasia of the samples. The expressions of proliferating cell nuclear antigen（PCNA） and bcl-2 of the samples were detected by immunohistochemistry. The apoptosis of vascular smooth muscle cells（VSMC） was detected by TUNEL. Results：Two weeks after vein grafting, compared with blank-control group and F-127 control group,intima hyperplasia was markedly inhibited by applying triptolide 300μg on adventitia（P〈0.05）, expressions of both PCNA and bcl-2 reduced significantly（P〈0.05）,and the positive cells of TUNEL increased markedly（P〈0.05）. Conclusion：Applying slow-releasing triptolide on adventitia by F-127 pluronic gel can effectively reduce VSMC proliferation and induce VSMC apoptosis,to inhibit intima hyperplasia of the vein grafts.