全反式维甲酸对球囊损伤大鼠胸主动脉内皮后内膜增生及PDGF-BB表达的影响

Effects of ATRA on Intimal Proliferation and Expression of PDGF-BB after Thoracic Aorta Balloon Injury in Rats

目的 研究全反式维甲酸 (all transretinoicacid ,ATRA)对球囊损伤大鼠胸主动脉内皮后内膜增生及血小板衍生生长因子B(BDGF BB)表达的影响。方法 球囊剥脱大鼠胸主动脉内皮 ,并随机将大鼠分为手术组、ATRA治疗组及对照组 ,各组大鼠均于术前 4d灌胃 ,分别在术后 2、7、14和 18d处死大鼠并摘除胸主动脉。通过组织学检查和免疫组化技术检测内膜增生情况、PDGF BB的表达及ATRA[30mg/ (kg·d) ]灌胃对它们的影响。结果 (1)对照组及内皮损伤后 2d均无血管内膜增厚 ,7d内膜开始增生 ,2 8d血管平滑肌细胞 (VSMCs)的增殖减弱 ,但细胞外基质增加 ,内膜继续增生 ;(2 )PDGF BB的表达于术后 2d开始升高 ,至 14d达高峰 ;(3)使用ATRA后内膜增生程度及PDGF BB的表达明显降低。结论 ATRA可有效地抑制血管损伤后内膜增生 ,其机制可能是通过抑制PDGF BB表达 。

Purpose: To investigate the effect of all-trans retinoic acid (ATRA) on intimal proliferation and expression of platelet derived growth factor BB(PDGF-BB) after vascular injury in rats. Methods: Make models of aortic endothelial denudation of rats by ballon catheter. Rats were randomly allocated into three groups;. Group 1 (n = 24) were given vascular balloon injury. Group 2 (n = 24) were given ATRA (30 mg/[kg&middotd]) into stomach from 4 days before injury to 28 days after injury. Group 3(n = 24) served as contrals were killed at day 2,7,14,28 after operation, not given vascular balloon injury. Neointima area were calculated morphologically at day 2,7,14,28 after injury. The expression of PDGF-BB were measured by means of immunohistochemical technique and imagine analyzer. Results: (1) The migration and proliferation of vascular smooth muscle cells (VSMCs) had not existed at day 2 after balloon injury and contral group. The thickening of intima had begun at day 7 after injury, and they were more significant at day 14. The proliferation of VSMCs decreased at day 28, but extracellular matrix increased and the intimal thickning continued. (2) The positive expression of PDGF-BB were found at day 2 after balloon injury and reached maximum at day 14. (3) When given ATRA, the neointimal area and the index of PDGF-BB expression reduced. Conclusions: ATRA can effectively repress intima proliferation after vascular injury, which may be associated with inhibiting the proliferation of vascular smooth muscle cells through down regulating the expression of PDGF-BB.