血管内皮生长因子在脑缺血耐受大鼠中的表达

EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN A RAT MODEL OF CEREBRAL ISCHEMIA TOLERANCE

目的检测局灶性脑缺血预处理诱导大鼠脑缺血耐受模型再灌注不同时间窗血管内皮生长因子(VEGF)的表达,探讨其在脑缺血耐受中的作用。方法将55只Wistar大鼠随机分成假手术对照组(SS+SS,5只)、假手术+再缺血组(SS+MCAO,25只)、缺血预处理+再缺血组(IP+MCAO,25只),后两组再随机分成5个亚组。线栓法阻塞大脑中动脉(MCAO)建立局灶性缺血预处理模型(缺血预处理10min),分别在缺血预处理后1、3、7、14、21d进行再次缺血2h再灌注22h,然后取脑检查。应用苏木精-伊红染色观察脑组织病理变化并测定脑梗死体积,观察神经行为缺损,免疫组化法检测VEGF蛋白表达。结果IP+MCAO组1、3、7d亚组与SS+MCAO组相应亚组比较,神经行为缺损评分明显降低,梗死体积明显减小,VEGF表达明显增高,差异均有显著性(t=2.357～11.479,P<0.05)。结论缺血预处理诱导了脑缺血耐受,预缺血诱导的VEGF表达增加在脑缺血耐受中发挥重要作用。

Objective To investigate the expression of vascular endothelial growth factor （VEGF） at different time points after reperfusion in a cerebral ischemia-tolerant rat model induced by focal ischemia preconditioning, and study the significance of VEGF in cerebral ischemia tolerance. Methods Fifty-five healthy Wistar rats were randomized to three groups： the sham operation group （SS＋SS,n=5）, the sham opertation and subsequent middle cerebral artery occlusion （MCAO） group （SS＋ MCAO,n--25）, and the ischemia preconditioning and subsequent MCAO group （IP＋MCAO,n=25）. The latter two groups were further divided into five subgroups. For ischemia preconditioning, the rats were performed MCAO with filament ligation for 10 min. On the 1st, 3rd, 7th, 14th and 21st day after ischemia preconditioning, the rats were given the second MCAO for 2 h followed by 22 h reperfusion. Brain tissues were biopsied and tissue sections stained with hematoxylin and eosin （HE） for histological study and determination of infarction volume. The models were evaluated with neurological deficit score. The expression of VEGF was determined by immunohistochemical staining. Results Compared with the corresponding subgroups of SS＋MCAO group, the neurologic scores were significantly reduced, the volume of cerebral infarction was significantly decreased and the expression of VEGF significantly increased in the 1st-, 3rd-and 7st day subgroups of IP＋MCAO group （t=2. 357-11. 479,P〈0.05）. Conclusion Ischemia preconditioning induced cerebral ischemia tolerance. IP induced up regulation of VEGF expression plays an important role in the induction of ischemia tolerance.