雷帕霉素对球囊损伤后血管平滑肌细胞表型及内膜增生的影响

目的建立大鼠腹主动脉球囊损伤模型,研究雷帕霉素对血管平滑肌细胞表型和内膜增生的影响。方法26只大鼠随机分为假手术组、球囊损伤组、羧甲基纤维素钠组和雷帕霉素组。雷帕霉素组行腹主动脉球囊损伤术前3天开始每天肌肉注射雷帕霉素0.5mgkg,术后连续14天每天肌肉注射雷帕霉素0.25mgkg。球囊损伤14天后进行电镜观察、组织学观察和形态学分析。结果假手术组电镜下血管平滑肌细胞呈收缩表型,球囊损伤后血管平滑肌细胞呈合成表型,雷帕霉素干预后血管平滑肌细胞电镜下表现介于两者之间。术后14天雷帕霉素组新生内膜面积比羧甲基纤维素钠组减少36.4%(0.14±0.03mm2比0.23±0.06mm2,P<0.01),内膜中膜比减少28.9%(17.7%±3.37%比28.86%±10.25%,P<0.01)。结论以上提示雷帕霉素可以抑制血管平滑肌细胞表型的改变,减轻球囊损伤后新生内膜的增生程度。

Effect of Rapamycin on Phenotype of Vascular Smooth Muscle Cell and Arterial Intimal Hyperplasia Post Balloon Injury in Rat

Aim To investigate the effect of rapamycin on phenotype of vascular smooth muscle cell(VSMC) and intimal hyperplasia in a rat model of restenosis post balloon injury. Methods Twenty-six healthy adult male rats were randomly divided into four groups: sham group (n=2), balloon group (n=8): received balloon injury only, cellulose group(n=8) received the vehicle solution, and rapamycin group(n=8) intramusclar administration of rapamycin (suspended in solution containing 0.2% sodium carboxymethyl cellulose) started 3 days before injury at a dose of 0.5 mg/kg and continued for 14 days at a dose of 0.25 mg/kg. Phenotype of VSMC was observed with electron microscope. Abdominal aortas were analyzed for intimal area, mean intimal thickness, media area and intimal/media area ratio. Results Electron microscope showed the morphilogic characteristics of VSMC changed from contractile to synthetic after balloon injury. VSMC showed less organelles and more myofilament when exposed to rapamycin. Neointimal area and intimal/media area ratio 14 days after injury showed a 36.4% and 28.9% reduce in the animals receiving rapamycin compared with those receiving cellulose respectively(0.14±0.03 mm 2 vs 0.23 ±0.06 mm 2 and 17.70%±3.37% vs 28.86%±10.25%, respectively, p<0.01). Conclusion Rapamycin can influence the phenotype transform of VSMC, and reduce the degree of neointimal hyperplasia.