G-CSF对脑出血大鼠血肿周围血管新生的作用机制研究  

Study on the effect and mechanism of granulocyte colony-stimulating factor on angiogenesis in perihematoma tissue in rat with intracerebral hemorrhage

作　　者：何晓英[1] 付华[2] 刘永刚[1] 李小刚[1] 

机构地区：[1]泸州医学院附属医院神经内科,四川泸州646000 [2]泸州医学院附属医院乳腺外,四川泸州646000

出　　处：《中风与神经疾病杂志》2014年第7期590-593,共4页Journal of Apoplexy and Nervous Diseases

基　　金：四川省卫生厅资助项目(编号110368);泸州市科技局资助项目(编号2011001)

摘　　要：目的观察粒细胞集落刺激因子(G-CSF)对脑出血(ICH)大鼠血肿周围血管新生的影响,并探讨其机制。方法 63只SD大鼠随机分为假手术组、ICH组、治疗组,每组21只。利用立体定位仪,向SD大鼠右侧苍白球注入断尾获取的自体动脉血制备ICH模型,治疗组于造模1 h后腹腔注射重组G-CSF60μg/kg,假手术组、ICH组经腹腔注射等量等渗盐水。3组大鼠于术后6 h、24 h、48 h、72 h、7 d、14 d、21 d进行神经功能障碍评分,后处死大鼠,免疫组化检测血肿周围CD34+血管数、VEGF的表达。结果治疗组大鼠从24 h开始各时间点神经功能障碍评分较ICH组明显增加(P<0.05)。假手术组见少许CD34+血管表达;ICH组6 h开始CD34+血管表达增多,14 d达高峰;治疗组各时间点CD34+血管表达较ICH组明显增多(P<0.05),高峰提前至7 d。假手术组见少量VEGF表达;ICH组6 h即出现VEGF表达增多,7~14 d达高峰;治疗组各时间点VEGF表达较ICH组明显增多(P<0.05),高峰提前至72 h^7 d。结论 G-CSF可上调ICH后VEGF表达,增加血肿周围新生血管生成,改善神经功能。Objective To investigate the effect of granulocyte colony-stimulating factor on angiogenesis in rat brain with intracerebral hemorrhage,and to explore its possible mechanism. Methods Sixty-three Spragne Dawley rats were ran- domly selected and divided into 3 groups ： sham operation, ICH group and treatment group. There were twenty-one rats in ev- ery group. Stereotaxic apparatus was used and fresh quantited autologous blood was infused into the right basal ganglia to build up rat experimental ICH model. Rats in the treatment group were administered rhG-CSF（60 μg/kg）by intraperitoneal injection 1 h after operation, while rats in ICH group and sham operation group were injected with equal volume of isotonic saline solution. Neural function defect of rats were assessed with Garcia＇ s score method on 6 h,24 h,48 h,72 h,7 d,14 d and 21 d after operation. Then the rats were sacrificed, CD34 positive microvascular and VEGF expression around hemato- ma in rats＇ brain were analyzed by immunohistochemistry at the same time point. Results The score of nerve function was obviously increased from 24 h in treatment group, and had significant difference compared with that of ICH group （ P 〈 O. 05）. The expression of CD34 positive microvascular was little in sham operation group. In ICH group,the expressions of CD34 positive microvascular were increaesed at 6 h and peaked at 14 d. Compared to ICH group, the expressions of CD34 positive microvascular in treatment group were increased at each time point（P 〈 0.05 ） and early peaked at 7 d. The expres- sion of ~EGF was little in sham operation group. In ICH group, the expression of VEGF increaesed at 6 h and peaked at 7 d - 14 d. At each time point, compared with the ICH group, the expression of VEGF in treatment group increased （P 〈 0.05） and peaked early at 72 h - 7 d. Conclusion G-CSF could promote angiogenesis by upregulating VEGF pathway to axert neurnnrotective effects.

关 键 词：粒细胞集落刺激因子 脑出血 血管内皮细胞生长因子 血管新生 

分 类 号：R743.34[医药卫生—神经病学与精神病学]