血管紧张素Ⅱ1型受体在血管球囊损伤后平滑肌细胞凋亡中的作用

Role of angiotensinⅡsubtype 1 receptor in smooth muscle cells apoptosis after balloon injury to vessel

目的 探讨血管球囊损伤后平滑肌细胞 (SMC)凋亡的机制。方法 采用末端脱氧核苷酸转移酶介导的三磷酸脱氧尿嘧啶缺口末端标记法 (TUNEL)和免疫组织化学技术检测球囊损伤后血管平滑肌细胞凋亡及血管紧张素Ⅱ 1型受体 (AT1 R)表达的变化。结果 球囊损伤后第 3天 ,血管中层AT1 R表达比假手术组显著增多 (P <0 0 5 ) ,以后无显著改变 ;损伤后第 7天内膜层AT1 R为中层的近 2倍 ;至损伤后第 2 8天 ,内膜层AT1 R表达最高 ;球囊损伤后第 3天 ,血管中层出现凋亡的SMC ;损伤后第 7天 ,内膜和中层SMC凋亡率最高 ,凋亡的SMC主要分布在内膜层 ;以后逐渐降低 ,至损伤后第 2 8天 ,仅内膜层有少量凋亡的SMC ,AT1 R拮抗剂Irbesartan显著增加SMC凋亡。结论 血管球囊损伤后 ,AT1 R上调 ,血管紧张素Ⅱ通过与AT1 R结合抑制VSMC凋亡。

Objective To investigate the mechanism of affecting smooth muscle cells apoptosis after balloon injury to vessel Methods The percentage of vascular smooth muscle cells (VSMC) apoptosis and the expression of angiotensin Ⅱ subtype 1 receptor (AT 1R) was measured by terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) and immunohistochemical technique after balloon injury Results Compared with sham's, the expression of AT 1R protein in vascular media was significantly increased at 3 days after balloon injury ( P <0 05), and then did not change significantly At 7 days, it was approximately twice in intima as that in media At 28 days it reached its peak VSMCs apoptosis occurred in vascular media at 3 days after balloon injury and reached a peak in media and intima where apoptosis was mainly present at 7 days, then decreased At 28 days after balloon injury, only a few apoptotic cells were in intima AT 1R antagonist (Irbesartan) significantly increased VSMCs apoptosis Conclusion AT 1R is upregulated after balloon injury and angiotensin Ⅱ inhibits VSMC apoptosis by combining with AT 1R