KLF4抑制球囊损伤诱导的新生内膜形成

目的： 通过腺病毒载体介导外源性KLF4在大鼠颈动脉球囊剥脱血管中进行表达，观察新生内膜增生情况，研究外源性KLF4对球囊损伤诱导的新生内膜形成的影响及初步探讨其机制。方法： 构建含有KLF4基因的重组腺病毒载体pAd-KLF4，将其导入内皮剥脱的血管壁。用HE染色观察血管新生内膜的厚度，免疫组织化学染色和RT-PCR分别检测外源性KLF4在血管中的表达以及与增殖和分化标志基因表达的关系。结果： 重组腺病毒pAd-KLF4可在血管壁中稳定表达KLF4。KLF4的过表达可显著抑制球囊损伤后血管新生内膜的增厚，转染pAd-KLF4的血管，其内膜/中膜比值（I/M）（0.52±0.15）明显小于pAd对照组（2.48±0.38）,P<0.05。pAd-KLF4组血管壁增殖标志蛋白PCNA和c-Jun表达也较pAd组明显降低（P<0.05）。结论： KLF4过表达可阻断损伤诱导的血管平滑肌细胞表型转化，进而抑制球囊剥脱后血管内膜的增生。

Exogenous KLF4 inhibits neointimal hyperplasia after balloon injury in rat

AIM: To observe the neointimal hyperplasia and to investigate the effect and mechanism of exogenous krüppel-like factor 4 (KLF4) on neointimal formation induced by balloon injury. METHODS: Adenovirus vector encoding the KLF4 (pAd-KLF4) was constructed and transfected into the balloon-injured carotid artery in rat. Neointima thickening was assessed using HE staining. Expression of exogenous KLF4 and the marker genes were detected by immunohistochemistry and RT-PCR. RESULTS: pAd-KLF4 stably expressed KLF4 protein in the transfected vascular wall. Overexpression of KLF4 significantly inhibited neointimal hyperplasia induced by balloon injury. The ratio of intima-to-media area (I/M) in pAd-KLF4 group (2.48±0.38) was significantly less than that in pAd group (0.52±0.15) (P<0.05). Proliferating cell nuclear antigen (PCNA) and c-Jun were significantly reduced in pAd-KLF4 group, compared with the pAd group (P<0.05). CONCLUSION: Overexpression of KLF4 inhibits the phenotype remodeling of vascular smooth muscle cells and neointimal hyperplasia induced by balloon injury.