外源性重组人促红细胞生成素对高氧脑损伤新生大鼠模型神经细胞凋亡及5-脂氧酶的影响  

Effects of exogenous recombinant human erythropoietin on neuronal apoptosis and 5 - lipoxygenase in neonatal rats with hyperoxia brain injury

作　　者：宋朝敏[1] 王程毅[2] 杨斌[1] 杨长仪[1] 王行富[3] 陈余朋[3] 

机构地区：[1]福建医科大学附属福建省妇幼保健院新生儿科,福州350001 [2]福建医科大学附属福建省妇幼保健院儿科,福州350001 [3]福建医科大学第一临床医学院病理科,福州350001

出　　处：《中华实用儿科临床杂志》2017年第6期461-464,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：福建省卫生厅青年科研课题（2013-1-12）;福建省妇幼保健院院内课题（09-13）

摘　　要：目的探讨外源性重组人促红细胞生成素（rhEPO）对新生大鼠高氧脑损伤后神经细胞凋亡的影响。方法将30只新生12 h内的Wistar大鼠按随机数字表法随机分为3组：rhEPO治疗＋800 mL/L高氧组（A组），9 g/L盐水＋800 mL/L高氧组（B组），9 g/L盐水＋空气组（C组）。A组每天给予颈后皮下注射rhEPO 1000IU/kg，共5 d。B组和C组给予同样剂量9 g/L盐水。A组和B组持续暴露于常压高氧模型舱中，维持容器内氧体积浓度为（800±30） mL/L，共5 d。实验过程中观察大鼠一般情况、体质量改变。5 d后处死全部大鼠，取脑组织，采用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法（TUNEL法）染色检测海马结构区细胞凋亡情况，免疫组织化学法测定海马结构区细胞5-脂氧酶表达。结果B组体质量增长和脑质量均低于C组，A组体质量增长和脑质量高于B组，差异均有统计学意义（F=11.179、8.140，均P〈0.05）。A组和B组发现海马结构区神经元细胞核部分固缩、深染，神经元排列松散，甚至局部神经元缺失、局灶性坏死，但A组较B组神经元密度大，坏死较少；C组海马结构区神经元细胞排列整齐，结构完整。B组海马结构区TUNEL染色阳性细胞数[（6.20±1.93）个/高倍视野]明显多于C组[（1.80±0.79）个/高倍视野]，A组海马结构区TUNEL染色阳性细胞数[（4.20±1.32）个/高倍视野]明显少于B组，差异有统计学意义（F=23.912，P〈0.05）。B组5-脂氧酶表达阳性细胞数[（6.90±1.29）个/高倍视野]明显多于C组[（1.00±0.67）个/高倍视野]，A组5-脂氧酶表达阳性细胞数[（5.60±0.97）个/高倍视野]少于B组，差异有统计学意义（F=95.044，P〈0.05）。结论rhEPO对新生大鼠高氧脑损伤具有脑保护作用，且可能通过干预5-脂氧酶途径减轻髙氧脑损伤引起的脑细胞凋亡。ObjectiveTo explore the effect of exogenous recombinant human erythropoietin （rhEPO） on neuronal apoptosis in neonatal rats after hyperoxia brain injury.MethodsThirty neonatal Wistar rats were randomly divided into 3 groups by random number table method： rhEPO treatment ＋ 800 mL/L hyperoxia group （group A）, 9 g/L saline ＋ 800 mL/L hyperoxia group （group B）, 9 g/L saline ＋ air group （group C）. Group A was given subcutaneous injection of rhEPO 1 000 IU/kg for 5 days.Group B and group C received the same dose of 9 g/L saline.Group A and group B were continuously exposed to atmospheric pressure hyperoxia model cabin to maintain the oxygen concentration in the container （800 ± 30） mL/L for 5 days.During the course of the experiment, the general situation and weight changes in rats were observed.After 5 d, all rats were sacrificed and brain tissues were taken.Neuronal apoptosis in hippocampal structural region of the newborn rats was observed by terminal deoxynucleotidyl transferase dUTP nick and labeling（TUNEL） staining.Immunohistochemical method was used to detect the expression of 5-lipoxygenase in hippocampal structural region of newborn rats.ResultsThe weight gain and brain weight of group B were lower than those of group C, the weight gain and brain weight of group A were higher than those of group B, and the differences were statistically significant（F=11.179, 8.140, all P〈0.05）. In group A and group B were found that the neuronal nucleus of the hippocampal neurons was partially contracted, deeply dyed, and the neuronal arrangement was loose, even with local neuron deletions and focal necrosis, but in group A neuron density was higher with less necrosis than that in group B. The neuronal cells in hippocampal structural region were neat and intact in group C. The number of TUNEL positive cells in hippocampal structural region of group B[（6.20±1.93） number/high power field] was significantly higher than that in group C [（1.80±0.79） number/high power field], the numb

关 键 词：重组人促红细胞生成素 脑损伤 高氧 大鼠 新生 神经保护 凋亡 5-脂氧酶 

分 类 号：R-332[医药卫生] R722.1