脑缺血耐受大鼠脑组织血管内皮生长因子和血管生成素-1表达的改变及其意义

Changes and their significances of the expression of vascular endothelial growth factor and angiopoietin-1 in brain tissue in rat with brain ischemic tolerance

目的探讨血管内皮生长因子(VEGF)和血管生成素-1(Ang-1)在短暂性脑缺血预处理(IP)诱导的脑缺血耐受大鼠脑组织表达的改变及其意义。方法将99只Wistar大鼠随机分成对照组(9只)、非IP(NIP)组(45只)和IP组(45只)。大脑中动脉线栓法建立局灶性IP模型,NIP组以假手术代替预缺血,分别在IP后1、3、7、14、21 d予以缺血2 h、再灌注22 h,对照组2次均为假手术。大鼠处死前给予神经功能缺损评分(NDS),采用TTC染色测定脑梗死体积,免疫组化染色法检测脑组织VEGF、Ang-1蛋白表达。结果对照组大鼠脑组织无梗死灶,NDS为0。IP 1、3、7 d亚组NDS和梗死体积显著小于NIP组1、3、7 d亚组(P<0.01～0.05),其中IP 3 d亚组NDS最低,梗死体积最小。对照组脑组织少量VEGF蛋白表达,IP 1、3、7 d亚组VEGF蛋白表达显著高于NIP 1、3、7 d亚组(均P<0.05),其中IP 3 d亚组VEGF蛋白表达最高。各组脑组织均有一定程度Ang-1蛋白表达,IP 7 d亚组Ang-1蛋白表达高于NIP 7 d亚组(P<0.05)。结论 IP 1～7 d内脑组织VEGF、Ang-1表达增加,对脑缺血耐受的产生具有重要作用。

Objective To investigate the changes and their significances of the expression of vascular endothelial growth factor （VEGF） and angiopoietin-1 （ Ang-1 ） in brain tissue in rat with brain ischemic tolerance induced by ischemic preconditioning. Methods Ninety-nine Wistar rats were randomly assigned to control group （n = 9）, non IP （NIP） group （n = 45 ） and IP group （n = 45）. The IP models were builded by occlusion of middle cerebral artery. Meanwhile, the rats in NIP group were received sham IP. The rats in IP and NIP group at 1, 3, 7, 14, 21 d after IP were ischemiaed again for 2 h and reperfusioned for 22 h. The control group was received sham operation twice. The neurological deficit scores （NDS） was evaluated before the rats scarificed. The cerebral infarct volume was detecd by TFC, and the expression of VEGF and Ang-1 protein in brain tissue were determined by immunohistochemical staining. Results In the control group, there was no infarct lesion in the brain tissue and NDS was O. NDS and infarct volume in IP 1, 3, 7 d subgroups were significantly less than those in NIP group 1, 3, 7 d subgroups （P 〈 0. 01 - 0. 05 ）. The lowest NDS and smallest infarct lesion were in IP 3 d subgroup. The expression of VEGF protein in brain tissue in control group was little. The expression of VEGF in IP 1, 3, 7 d subgroups were significantly higher than those in NIP group 1, 3, 7 d subgroups （ all P 〈 0.05 ） , and which in IP 3 d subgroup was the highest. The expression of Ang-1 protein in brain tissue in each group was observed, but which in IP 7 d subgroup was significantly higher than that in NIP 7 d subgroup （P 〈 0. 05 ）. Conclusion After 1 - 7 d of IP, the expression of VEGF and Ang-1 protein in brain tissue are increased and which has very important roles to caused brain ischemic tolerance.