Toll样受体4在新生小鼠常压高氧脑损伤中的作用  

Roles of Toll-like receptor 4 in hyperoxia-induced brain injury in the newborn mouse

作　　者：陈坤[1] 蒋朴[1] 徐颖[1] 幸宇[1] 邓世雄[1] 

机构地区：[1]重庆医科大学附属第一医院党办,400038

出　　处：《免疫学杂志》2012年第2期98-103,共6页Immunological Journal

基　　金：中国博士后基金(20090450790)

摘　　要：目的探讨Toll样受体4(Toll-like receptor 4,TLR4)在新生小鼠常压高氧脑损伤中的作用。方法新生3 d(P3)的TLR4野生型(W)和TLR4突变型(M)小鼠各36只,随机分为:100%高氧暴露组(WO2组,MO2组)及空气对照组(WA组,MA组),每组18只。高氧暴露组置于100%高氧箱中2 d,以空气中常规饲养的同龄小鼠作为空气对照组。各组于P6随机取12只小鼠脑组织,用于检测TLR4 mRNA表达及石蜡切片,染色观测神经细胞密度,并检测细胞凋亡情况;其余小鼠饲养至28 d,Morris水迷宫实验评价各组小鼠学习记忆能力。结果 RT-PCR提示WO2组TLR4 mRNA表达较WA组明显增加(P<0.05);染色WO2组在前额叶皮质区平均光密度低于WA组(P<0.05)及MO2组(P<0.05),在海马CA1区小于WA组(P<0.05),在两区凋亡细胞指数均较WA组及MO2组增高(P<0.05);MO2组与MA组比较,各个脑区神经细胞密度及凋亡指数均无明显差异(P>0.05)。Morris水迷宫WO2组与WA组比较,逃避潜伏期延长(P<0.05),目标象限停留时间缩短(P<0.05),穿越虚拟平台次数减少(P<0.05)。MO2组与MA组比较,上述各项指标均无明显差异。结论 TLR4功能缺失可减少高氧导致的未成熟神经细胞凋亡,降低新生期高氧暴露对远期学习记忆能力的损害。To explore the role of Toll-like receptor 4 on immature brain injury in the newborn mouse after hyperoxia exposure,we selected 72 postnatal 3 d mice,including 36 TLR4 wild-type（W） and 36 TLR4 mutant mice（M）,which were randomly divided into hyperoxia group exposed in 100% oxygen for 2 d（WO2,MO2） and control group exposed in the air（WA,MA）（n = 18） respectively.At postnatal 6 d,12 mice of each group were randomly selected,among which brain tissues of 6 mice were utilized for detection of TLR mRNA expression by RT-PCR,brain of the other 6 mice were removed and fixed for crystal violet staining in order to estimate neuronal density in prefrontal cortex and hippocampus CA1,and for in situ death detection using terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling（TUNEL） reaction.The remaining 6 mice in each group were bred until postnatal 28 d for Morris water maze.We found that in WO2 group,the expression of TLR4 mRNA was increased compared to MA group,the neuronal density（mean optical density,MOD） of prefrontal cortex were significantly decreased compared to WA group and MO2 group（P 〈 0.05）,the neuronal density of hippocampus CA1 was decreased compared to WA group（P 〈 0.05）,the apoptosis index of the two areas were increased compared to WA group and MO2 group（P 〈 0.05）.Furthermore,neuronal density and apoptosis index of all different encephalic regions were on significant difference（P 〉 0.05）.The time of escape latency of WO2 group after trains was longer than that of control group（P 〈 0.05）,while the time in target quadrant and the number of times through virtual platform were smaller compared to that of the control（P 〈 0.05）.Nevertheless,indexes mentioned above did not demonstrate significant difference between MO2 group and MA group.Our results suggest that TLR4 singling may be involved in hyperoxia-induced immature brain injury.And loss of normal function of TLR4 could alleviate the neuronal loss,apoptosis,and behavior performance depr

关 键 词：TOLL样受体4 高氧症 脑损伤 凋亡 水迷宫 

分 类 号：R722.1[医药卫生—儿科]