内皮祖细胞对慢性脑缺血大鼠空间学习记忆影响的机制研究

目的 探讨自体移植内皮祖细胞对慢性脑缺血大鼠行为学习功能的影响.方法 制作慢性脑缺血大鼠模型,静脉自体移植内皮祖细胞,进行水迷宫检测学习记忆功能,并从脑缺血区新生细胞、脑部血管、血管内皮生长因子(VEGF)等方面探讨可能的机制.结果 ①Morris水迷宫实验中,训练第2～5天的逃避潜伏期实验组(EPC组)[分别为(44.45 ±9.44)s,(38.32±1.51)s,(34.95±6.76)s,(24.46±5.47)s明显短于对照组(PBS组)[对应为(52.79 ±6.47)s,(43.15±11.21)s,(50.29±11.41)s,(53.75±7.35)s](P＜0.01);第一象限游泳时间EPC组(26.76±3.79)s明显长于PBS组[(14.28±2.40)s],(P＜0.0).②缺血脑组织内的BrdU阳性细胞数PBS组为(12.17±3.49)个,实验组为(26.8±5.76)个,差异有显著性(P＜0.05).③脑血管共聚焦检测结果显示:EPC组较PBS组比较毛细血管内径显著性变小(分别为(2.8±0.2)μm与(3.4±0.24)μm,同源组织缺血边界地区的分支点数目显著增加[(分别为:(210.1±13.80)与(164.2±12.3)],EPC组可以显著增加微血管总面积(分别为:(84365±3897)与(74568±4626)μm2/0.002mm3),P＜0.05].④大鼠血浆VEGF检测[分别为(63.91±6.71)pg/ml;(21.81 ±4.25)pg/ml,P＜0.05]显示干预组明显增加(P＜0.05).结论 内皮祖细胞可以显著改善慢性脑缺血大鼠的学习记忆行为能力,其可能的机制是VEGF相关联的神经保护和血管再生,在治疗慢性脑缺血疾病中有着很大的应用前景.

Behavioral studies on the effect of endothelial progenitor cells on the spatial learning and memory of chronic cerebral ischemic rats

Objective To study the effect of endothelial progenitor cells on the behavior of chronic cerebral ischemic rats. Methods Adult rats were treated using the protocol of chronic cerebral ischemic model. Then translated the endothelial progenitor cells in vein to them, and Morris water maze was carried out to test the learning and merrory ability of the rats. The cell proliferation, vascular distribution and the plasma VEGF levels were day of 2nd to 5th of experimental group ( EPC group ) were significantly shorter than the control group ( PBS group), which were(44.45 ±9.44)s,(38.32±1.51)s,(34.95 ±6.76)s,(24.46 ±5.47)s and (52.79±6.47 ) s, ( 43.15 ± 11.21 ) s, ( 50.29 ± 11.41 ) s, ( 53.75 ± 7.35 ) s, (P ＜ 0.01 ) respectively. The time of EPC group spend in the first quadrant were significantly longer than that of the PBS group, which were (26. 76 ±of the EPC group( 26.8 ± 5.76 ) was higher than that of the conrespondering areas in the control group( 12.17 ±ments of capillaries were (P＜0.05) shorter in the PBS groups( (3.4 ±0.24) μm) than in the EPC groups( (2.8± 0.2 )μm) significantly, EPC group could significantly (P ＜ 0.05 ) increased the number of branch points in the boundary regions of ischemia compared with the number in the PBS group (respectively (210. 1 ± 13.80 ) and (164.2 ± 12.3 )). Three-dimensional cerebral vessel surface area in the ipsilateral hemisphere significantly increased in the EPC group compared with the PBS group (respectively (84365 ± 3897 )μm2/0. 002mm3 and group in the plasma VEGF levels ( ( 63.91 ± 6.71 ) pg/ml; ( 21. 81 ± 4.25 ) pg/ml, respectively (P ＜ 0.05, P ＜0.01 ). Conclusion There are positive behavioral effects of endotbelial progenitor cells in chronic cerebral ischemic rats. The possible mechanisns mavbe involve the nerve protection and regeneration of the vascular associated with the VEGF. The endothelial progenitor cells maybe have a great prospect in the therapy of chronic cerebral ischemic disease.