大鼠脑出血周边组织脑水含量、细胞凋亡和Bax表达的变化及粒细胞集落刺激因子的影响  

Changes of brain water content,apoptosis and expression of Bax around hematoma and the effect of granulocyte colony stimulating factor on acute intracerebral hemorrhage in rats

作　　者：关雪莲[1] 侯丽淳[1] 毕胜[1] 曲红玉[2] 杨慧[1] 李培育[1] 张佳月[1] 王复新[1] 

机构地区：[1]佳木斯大学附属第一医院神经内科,黑龙江佳木斯154003 [2]佳木斯大学附属第一医院心内科,黑龙江佳木斯154003

出　　处：《中风与神经疾病杂志》2015年第4期328-331,共4页Journal of Apoplexy and Nervous Diseases

基　　金：黑龙江省教育厅科学技术研究项目基金资助(No.12531716)

摘　　要：目的研究粒细胞集落刺激因子(G-CSF)对脑出血(ICH)大鼠神经功能损伤、脑水肿的影响,粒细胞集落刺激因子对大鼠脑出血周边组织Bax表达及细胞凋亡的影响。方法 Wistar大鼠112只,随机分为脑出血组、脑出血+G-CSF组,两组各分为(出血前、出血后4 h、6 h、12 h、24 h、72 h、7 d)7个时间点。免疫组化法测定大鼠脑出血周边组织Bax的表达,利用原位末端标记法测定出血周边组织中神经细胞的凋亡情况。并在脑出血后24 h、48 h、72 h、7 d测定大鼠神经功能评分和脑含水量。结果脑出血后24 h开始大鼠就出现明显的神经功能缺失症状,G-CSF治疗后神经功能缺失症状得到明显改善,在1 w内的各个时间点两组比较差异有显著性(P<0.01)。脑出血大鼠24 h即出现脑水肿,脑水肿形成的高峰时间在ICH后48 h^7 d左右,ICH大鼠在G-CSF治疗后脑水肿形成明显减轻,两组间比较差异有显著性(P<0.05;P<0.01)。大鼠脑出血周边组织Bax表达4 h开始升高(P<0.01),大约24 h左右Bax表达达峰值。大鼠脑出血周边组织6 h出现凋亡细胞,12 h上升显著(P<0.01),3 d达峰值,7 d时仍存在较多凋亡细胞。G-CSF干预后,Bax表达及凋亡细胞数量与脑出血组对应时间点比较显著下降(P<0.01)。结论脑出血大鼠出现明显脑水肿和神经功能损伤,脑出血周边组织神经细胞存在长时间凋亡。G-CSF可抑制大鼠脑出血后Bax蛋白表达,从而抑制神经细胞凋亡。Objective To study the effects of granulocyte colony stimulating factor in dynamic changes of behavior,cerebral edema,expression of Bax and apoptosis around hematoma of acute intracerebral hemorrhage（ ICH） and the relationship between them. Methods 112 Wistar rats were randomly divided into ICH group and ICH ＋ G-CSF group. The two groups were divided by time points（ before ICH,4 h,6 h,12 h,24 h,72 h and 7 d after ICH）. The rats were performed behavioral test and detected cerebral edema on 1 d,2 d,3 d,and 7 d after ICH. The expression of Bax around hematoma in ICH was analyzed by immunohistochemistry. By terminal deoxynucleotidyl transferase-mediated d UTP nick end labeling（ TUNEL） method,the changes of apoptosis cells around hematoma on ICH were determined. Results Cerebral edema peaked around the third day after ICH and remained for more than a week. G-CSF signifieantly significantly improved the neurology dysfunction of rats through the decreased scores of behavioral test and brain edema was also attenuated（ P〈0. 05,P〈0. 01）. The expression of Bax around hematoma on ICH begin began to increase at 4 h（ P〈0. 01）,reached the top at about 24 h. The apoptosis around hematoma of ICH was detected at 6 h and peakeding at 12 h（ P〈0. 01）. Until 7 d there still had still been more apoptosis. The expression of Bax and apoptosis significantly decreased compared at the same time after G-CSF interference around hematoma of ICH（ P〈0. 01）. Conclusion The neurology dysfunction and brain edema were presented obviously in ICH rats,the apoptosis lasted long time around hematoma on ICH. There was an inhibitory effect of GCSFG-CSF on expressions of Bax protein following intracerebral hemorrhage in rats,which can inhibit neuronal apoptosis.

关 键 词：脑出血 BAX 脑水含量 细胞凋亡 粒细胞集落刺激因子 

分 类 号：R743.34[医药卫生—神经病学与精神病学]