摘要
目的探讨脑性瘫痪(cerebral palsy,CP)发生的炎症细胞因子网络调控机制。方法 30只出生7日龄清洁级健康雄性SD大鼠按随机数字表法分为2组:CP模型组和对照组,每组15只。应用一侧颈总动脉结扎结合缺氧的方法构建CP大鼠模型,即幼鼠结扎右颈总动脉结合体积分数为0.08的O2与体积分数为0.92的N2缺氧环境的方法制作幼鼠CP模型。对照组仅切开幼鼠颈部皮肤后缝合皮肤伤口,未置于缺氧环境。幼鼠CP模型构建术后3w,采用足印步态重复间距试验、平衡木试验检测鼠的运动功能,进行行为学评价;取鼠脑组织行苏木精-伊红染色观察脑组织病理变化,以行为学评价和病理检测结果鉴定CP模型是否构建成功。分别取成功构建的CP模型组和对照组大鼠脑白质和脑皮层组织,应用炎症细胞因子与受体基因芯片进行基因表达检测,绘制基因表达谱,筛选有表达差异的基因。结果应用一侧颈总动脉结扎结合缺氧的方法成功建立了大鼠CP模型;与对照组相比,CP模型组脑白质和脑皮层组织中表达上调的促炎性反应细胞因子与受体基因分别有10个和8个(P<0.05),表达下调的抗炎细胞因子与受体基因分别有3个和2个(P<0.05)。结论 CP大鼠脑白质和脑皮层存在促炎症细胞因子基因表达上调,抗炎症细胞因子基因表达下调,从而导致促-抗炎性细胞因子网络和促-抗炎性反应体系平衡失调,这可能是CP发生中出现高促炎性反应状态的原因和新机制。
Objective To investigate the mechanism of inflammatory cytokine network in the development of cerebral palsy（CP）. Methods 30 healthy male Sprague Dawley 7 day-old neonatal rats were randomly divided into two groups：CP model group and control group, 15 rats each group. Rats in the model group were ligated at the right common carotid artery,followed by exposure to hypoxia（0.08 volume fraction of 02 and 0. 92 volume fraction of N2）for 2 h. Rats in the control group only incised the anterior cervical skin. The results of the repeated gait intervals and the time of crossing balancing beam and the histological changes via hematoxylin eosin stain were used to prove the successful CP model 3 weeks after operation. Gene expression profiles of rat cerebral white matter and cerebral cortex tissues from each group were analyzed by using inflammatory cytokines and receptors cDNA microarrays, respectively. Differentially expressed genes were screened. Results CP model using unilateral common carotid artery ligation and hypoxia was successfully established through the results of the gait repeated interval and the time of crossing balancing beam and the histological changes via hematoxylin-eosin stain. Compared with the control group, there were 10 and 8 differentially up-regulated expressed pro-inflammatory genes and receptors, ewapectively（P〈 0.05） ,and 3 down-regulated anti-inflammatory genes in rat cerebral white matter and cerebral cortex tissues in the CP model group（P〈0. 05）. Conclusions Gene expression of pro-inflammatory cytokines and receptors was upregulated in the cerebral white matter and cerebral cortex tissues of the CP rats,which may eventually contribute to disequilibrium of the network of pro- and anti-inflammatory cytokines and receptors and disequilibrium of response of pro-and anti-inflammatory system and high inflammatory response state, thus providing new mechanistic insight into CP.
出处
《成都医学院学报》
CAS
2012年第4期508-511,共4页
Journal of Chengdu Medical College
基金
国家自然科学基金(NO:81102541)
国家十二五支撑课题(2013BAI01B003)
国家中医药管理局"十二五"重点学科中医儿科学项目
关键词
脑性瘫痪
大鼠
缺氧缺血模型
基因芯片
炎症细胞因子与受体
脑白质
脑皮层
Cerebral palsy
Rat
Hypoxia-ischemia model
Gene chip
Inflammatory cytokins and receptors
Cerebral white matter
Cerebral cortex
