联合应用促红细胞生成素和粒细胞集落刺激因子对早产鼠缺氧缺血性脑损伤的保护作用  

Protective Effect of Combined Application of Erythropoietin and Granulocyte Colony-Stimulating Factor in Experimental Premature Rat with Hypoxia-Ischemia Brain Damage

作　　者：周卓妍[1] 宋燕燕[2] 林兴会[1] 赵小朋[2] 吕俊健[2] 叶青青[2] 杨默[3] 

机构地区：[1]暨南大学医学院生理学教研室,广州510632 [2]广州市妇婴医院儿科,广州510180 [3]香港大学医学院儿科学系,中国香港

出　　处：《实用儿科临床杂志》2008年第6期425-427,440,共4页Journal of Applied Clinical Pediatrics

基　　金：广东省自然科学基金项目资助(5013928)

摘　　要：目的探讨联合应用促红细胞生成素(EPO)和粒细胞集落刺激因子(G-CSF)对早产鼠缺氧缺血性脑损伤(HIBD)模型的神经保护作用。方法将7日龄早产鼠结扎右侧颈总动脉,置80 mL/L氧环境中放置2 h,制备HIBD模型。实验分为假手术组、对照组、EPO治疗组、G-CSF治疗组和EPO加G-CSF联合治疗组。EPO、G-CSF及EPO加G-CSF治疗组分别于进缺氧仓前30 min、出缺氧仓后即刻及以后1次/d腹腔注射EPO(5 000 IU/kg),G-CSF(50μg/kg),以及EPO(5 000 IU/kg)加G-CSF(50μg/kg),连续1周。假手术组不予任何药物,对照组为相同时间点腹腔注射磷酸盐缓冲液(PBS)。通过测量各组脑质量、脑损伤比率、组织学检查及姿势反射实验观察EPO、G-CSF及EPO加G-CSF联合应用的疗效。采用SPSS10.0软件进行统计学分析。结果对照组一般情况无明显改变,术后1周及3周脑质量减低明显,脑损伤比率明显大于假手术组(P<0.001,0.01),形态学发现大脑半球出现明显萎缩,有神经元变性坏死。术后3周姿势反射正常率明显低于假手术组(P<0.001)。经EPO,G-CSF及EPO加G-CSF处理后,与对照组比较,各治疗组早产鼠脑质量有所增加(P<0.05,0.01),脑损伤比率明显减小(P<0.05,0.01),形态学发现大脑皮质萎缩程度均有不同程度的减小,神经元变性及脱失较对照组减轻。术后3周姿势反射实验正常率明显提高(P<0.05)。结论EPO和G-CSF对早产鼠HIBD具有一定神经保护作用,二者联合应用可达到更好保护效果。Objective To explore the neuroprotective effect of combined application of erythropoietin （ EPO ） and granulocyte - colony stimulating factor（ G - CSF） in experimental premature rats with hypoxia - ischemia brain damage （HIBD）. Methods HIBD was induced in premature rats on 7 days postnatal age by ligation of fight common carotid artery, followed by 2 hours of hypoxia（ 80 mL/L O2 ）. The subjects were divided into sham- operated group, control group, EPO treatment group, G- CSF treatment group and EPO and G -CSF treatment group. EPO 5 000 IU/kg, G - CSF 50 μg/kg and EPO 5 000 IU/kg, and G - CSF 50 μg/kg were injected 30 min pre - hypoxia, after - hypoxia and daily from 2 d post -surgery for 7 d. Phosphate buffer solutins（PBS） was injected in crntrol group at the same time. There was no injection in spam - operated group. The neuroprotective effects of EPO, G - CSF and combined application of both on premature rats HIBD model were detected by brain weight, the difference in weights between the ipsilateral （right） and contralateral （left） brain , ratio of brain damnification, histology and function test. Results There were no significant changes in general status in control group. The significant brain injury in the control group was observed and measured by reduction in relative weights of ipsilateral to contralateral （ P 〈 0. 001,0.01 ）, ratio of brain damnification （ P 〈 0. 001,0.01 ） and compromised sensorimotor functions in response to postural reflex test（ P 〈 0. 001 ）, compared with those of sham - operated rats. Histopathological evaluation demonstrated that there were atrophy of hemisphere, neuron edema and necrosis. Treatments with EPO, G - CSF, EPO and G - CSF could significantly reduced severity of brain injury, indicated by increasing ipsilateral brain relative weight and neuron density （P 〈0.05, 0.01 ）, decreasing the ratio of brain damnification （P 〈0.05, 0.01 ）. Histopathological evaluation demonstrated that there was decrease of atrophy of h

关 键 词：促红细胞生成素 粒细胞集落刺激因子 神经保护 鼠 早产 脑损伤 缺氧缺血 

分 类 号：R722.6[医药卫生—儿科]