罗格列酮对CD34修饰脱细胞血管支架体内生长的影响

Effect of rosiglitazone on the growth of CD34 modified decellularized vascular scaffold in vivo

背景:早期研制的脱细胞血管基质支架上预载CD34+抗体会促进其再内皮化,但同时会加重支架内血管内膜增生。国内外研究证实过氧化物酶增殖体受体γ激动剂罗格列酮在体外可抑制平滑肌细胞增生及迁移,可减少血管损伤处内膜增生。目的:进一步验证过氧化物酶增殖体受体γ激动剂罗格列酮对CD34抗体修饰脱细胞血管支架体内移植后平滑肌细胞生长及内膜增生的影响。方法:获取新鲜兔颈动脉,应用光化学偶联法将CD34抗体固定到去细胞光氧化的血管支架上,构建抗体修饰的组织工程血管。将制备的血管分别移植于实验兔的颈动脉上,其中对照组予以移植单纯光氧化处理的脱细胞血管,CD34组予以CD34抗体预载的血管,罗格列酮组移植CD34抗体预载的血管并予喂养罗格列酮。结果与结论:移植后10d:对照组移植血管内皮样细胞数量稀少,CD34组和罗格列酮组可见较多的内皮样细胞覆盖;CD34组血管内膜较罗格列酮组厚,α-SMA染色显示CD34组血管平滑肌细胞数量较后者为多,其差异有显著性意义。移植后30d:CD34组和罗格列酮组血管内皮样细胞基本覆盖管腔全层,对照组内皮样细胞数量仍较少;另外,CD34组血管内膜及管壁中可见大量的平滑肌样细胞及细胞外基质沉积,而罗格列酮组血管结构中平滑肌样细胞数量相对较少,内膜增生亦较轻。提示CD34修饰脱细胞血管支架可促进其内皮细胞的增生,罗格列酮可抑制血管支架中平滑肌细胞的增殖,减少内膜增生。

BACKGROUND：CD34 antibodymodification can promote the reendothelialization of decellularized vascular scaffold,but it can also increase the intima hyperplasia.Related studies in China confirm that rosiglitazone as a type of peroxisome proliferator activated receptor-γ（PPAR-γ） agonist can inhibit the hyperplasia and migration of smooth muscle cells in vivo and reduce intima hyperplasia in vascular injury region.OBJECTIVE：To further verify the effect of rosiglitazone as a type of PPAR-γ agonist on the growth of smooth muscle cells and intima hyperplasia after transplantation of CD34 antibody modified decellularized vascular scaffold in vivo.METHODS：Fresh carotid arteries from rabbits were involved.CD34 antibody was fixed onto the decellularized vascular scaffolds using photochemical coupling to construct modified tissue engineering vascular which were transplanted into the carotid arteries of the experimental rabbits.Oxidation-treated vascular were transplanted into the control group.CD34 antibody modified vascular were transplanted into the CD34 group and rosiglitazone group,besides,the rosiglitazone group were treated with rosiglitazone.RESULTS AND CONCLUSION：After transplantation of 10 days,there was few endothelial cells in the transplanted vascular of the control group and more endothelial cells in the CD34 group and the rosiglitazone group,and the intima in the CD34 group was thicker than that in the rosiglitazone group.Alpha-smooth muscle actin showed that the smooth muscle cells in the CD34 group are obviously more than that in the rosiglitazone group.At 30 days,the endothelial cells almost overlaid the whole lining endothelium in the CD34 group and the rosiglitazone group,but the number of endothelial cells in the control group was still small.There were much more smooth muscle-like cells and extracellular matrix in the CD34 group.CD34 antibody-modification can promote the re-endothelialization of decellularized vascular,and rosiglitazone can inhibit the hyperplasia of smooth miscle cells and reduce the intima hyperplasia.