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不同途径导入rAAV-VEGF165基因对大鼠脑缺血边缘区血管生成的影响
Experimental studies on the different route of gene transfer of rAAV-VEGF165into ischemic rat brain to affect the angiogenesis in the ischemic penumbra in rats
【摘要】 目的探讨脑池内及静脉导入重组腺病毒介导血管内皮细胞生长因子(rAAV—VEGF165)基因对大鼠脑缺血边缘区血管生成的影响。方法用线栓加环扎法建立SD大鼠持续性大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型。SD大鼠48只,随机分为脑脊液导入组、静脉导入组、单纯梗死组和假手术组,治疗组于术后24h内将rAAV—VEGF165基因通过小脑延髓池或静脉内导入。各组分别于7d和14d断头取脑,CD31免疫组化染色检测脑组织微血管密度。结果各组脑缺血边缘区CD31阳性细胞密度(个/高倍视野,×200)分别为:7d 组:脑脊液导入组92.73±5.18、静脉导入组77.40±5.43、单纯梗死组46.50±5.33和假手术组13.90±1.49(P< 0.05);14d组:脑脊液导入组104.05±4.30、静脉导入组89.88±5.77、单纯梗死组65.33±2.31和假手术组13.90± 1.49(P<0.05)。结论 rAAV—VEGF165基因可以通过脑池内及静脉内导入转染到大鼠缺血脑组织中并表达 VEGF,促进新生血管的形成和侧支循环的建立,治疗脑缺血。
【Abstract】 Objective To investigate the effect of recombinant adeno-associated virus mediated vascular en-dothelial growth factor 165 gene (rAAV-VEGF165) on angiogenesis in the ischemic penumbra in rats by cere-brospinal fluid (CSF) or intravenous route. Methods After establishing a rat model of permanent middle cerebral artery occlusion (MACO) by nylon suture embolization and cerclage,the rAAV-VEGF165gene was injected through CSF or intravenous in 24 hours. On the 7th and 14th day,the rats were killed,microvessel density was assessed with CD34 immunohistochemistry. Results The density of CD31-IR-positive cell (under high power field, ×200) in the cerebral ischemic penumbra of each group at the 7th day was 92. 73±5. 18 in CSF group, 77. 40±5. 43 in intravenous group,46. 50±5. 33 in MCAO group and 13. 90±1. 49 in sham-operation group respectively(P<0. 05)s and at the 14th day was 104. 05±4. 30 in CSF group,89. 88 ± 5. 77 in intravenous group,65. 33 ± 2. 31 in MCAO group and 13. 08±1. 90 in sham-operation group respectively(P<0. 05). Conclusion The rAAV-VEGF165 can be transfected into the cerebral ischemic tissue through both CSF route and intravenous route to express VEGF,which can promote the formation of new vessels and protect neurocytes in cerebral ischemic disease.
- 【文献出处】 中风与神经疾病杂志 ,Journal of Apoplexy and Nervous Diseases , 编辑部邮箱 ,2006年02期
- 【分类号】R743
- 【被引频次】6
- 【下载频次】146