经外膜缓释雷公藤内酯醇抑制自体移植静脉内膜增生

Adventitia applied slow-releasing triptolide inhibits intima hyperplasia in vein graft

目的探讨经外膜缓释雷公藤内酯醇(triptolide)对自体移植静脉内膜增生的抑制作用。方法健康雄性新西兰大白兔24只,建立颈外静脉-颈总动脉移植模型。随机将动物等分为3组。空白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20%F-127多聚凝胶0.5mL,实验组在移植血管外膜喷洒携带雷公藤内酯醇300μg的F-127多聚凝胶0.5mL。术后2周取标本。用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bcl-2和Fas的表达,TUNEL法检测标本中血管平滑肌细胞(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,实验组血管内膜增生明显受抑制(P<0.05),bcl-2的表达[(18.2±8.4)%]显著减少,而Fas的表达[(21.4±8.9)%]显著增加,凋亡细胞[(28.4±7.6)%]也显著增加(P<0.05)。结论经外膜缓释雷公藤内酯醇可有效抑制移植静脉内膜增生,这一作用可能系通过促进VSMC凋亡而实现的。

Objective To investigate the inhibitory effect of appling slow-releasing triptolide on adventitia on the intima hyperplasia of autologous vein graft. Methods In 24 male New Zealand rabbits, external jugular vein to common carotid artery models were established, and then were divided into 3 equal groups at random ： blank-control group, receiving no management on adventitia of the vein graft; F-127 control group, receiving local application of 0. 5 mL of 20 % F- 127 on adventitia of the vein graft ; experiment group, receiving local application of 0. 5 mL of 20 % F-127 containing triptolide 300μg. Vein graft specimens were harvested at 2 weeks after the operation. Histomorphologic methods were used to detect the degree of intima hyperplasia of the specimens. The expression of bcl-2 and Fas of the specimens was detected by immunohistochemistry. The apoptosis vascular smooth muscle cells （VSMC） were detected by TUNEL. Results Two weeks after vein grafting, compared to blank-control group and F-127 control group, intima hyperplasia of experiment group [ intima thickness （ 29.9± 7.6 ） μm, I/M 0.56 ± 0.08 ] was markedly inhibited （ P 〈0. 05 ）. Expression of bcl-2 [ （ 18. 2 ±8. 4 ） % ] was reduced significantly, however, expression of Fas （ 21 . 4 ± 8. 9 ） % increased markedly, and the apoptotic cells [ （ 28. 4 ± 7.6 ） % ] also increased markedly （P 〈 0. 05 ）. Conclusions Applied slow-releasing triptolide by F-127 pluronic on the vein graft adventitia can effectively inhibit intima hyperplasia of vein graft by a mechanism of enhancement of VSMC apoptosis