目的 探讨缺血性脑卒中大鼠缺血周边脑组织Caveolin-1(Cav-1)的表达及抑制其表达对缺血周边血管新生的影响。方法 随机将雄性Wistar大鼠分为4组:假手术组(Sham组,n=15),脑缺血组(MCAO组,n=55),Cav-1 siRNA慢病毒转染组(siRNA组,n=20)以及非编码siRNA慢病毒转染组(misRNA组,n=20)。用Q-PCR以及免疫印迹检测Cav-1的动态表达,FITC-dextran检测血管密度,多普勒血流仪检测血流量。结果 与Sham组比较,MCAO组再灌注4 h~3 d,Cav-1表达逐渐下降(P均〈0.05),3 d表达水平最低(P〈0.01),7 d后明显恢复(P〈0.05),14 d接近正常(P〉0.05)。与MCAO组比较,siRNA组Cav-1的表达水平显著降低,并且缺血周边血管密度及血流量显著下降(P均〈0.05);misRNA组的上述指标无明显变化。结论 Cav-1参与调节缺血性脑卒中后缺血周边脑组织的血管新生。
Objective To investigate the expression and involvement of Caveolin-1( Cav-1) in postischemic angiogenesis using a rat model of ischemic stroke. Methods Normal male Wistar rats were randomly divided into four groups:Sham group( n = 15),cerebral ischemia group( MCAO group,n = 55),lentivirus-expressing Cav-1 siRNA treated group( siRNA group,n = 20) and lentivirus-expressing nonsense siRNA treated group( misRNA group,n = 20).Q-PCR and Western blotting analysis were used to detect the expression of Cav-1. FITC-dextran was used to detect the vessel volume,and Laser Doppler was used to measure the local cerebral blood flowin ischemic penumbral. Results The expressions of Cav-1 from hour 4 to day 3 post-MCAO significantly decreased in MCAO group( all P〈0. 05),compared with sham group,and the minimum level appeared on day 3 post-MCAO( P〈0. 01). Interestingly,the expression of Cav-1 on day 7 post-MCAO significantly restored( P〈0. 05),and reached the normal level on day 14post-MCAO( P〉0. 05). As expected,in Cav-1 siRNA group,the expression of Cav-1 significantly decreased compared with MCAO or misRNA group( all P〈0. 05). Meanwhile,there were significantly weakened vessel volume and local cerebral blood flowin ischemic penumbral( P〈0. 05). Conclusion Cav-1 might be involved in postischemic angiogenesis. Further investigation of the regulation molecular machenism of Cav-1 in postischemic angiogenesis may be helpful for therapeutic angiogenesis for ischemic stroke.