促红细胞生成素对新生大鼠感染性脑损伤后神经细胞增生与凋亡的影响  

Effects of erythropoietin on neuronal proliferation and apoptosis in neonatal rats after infection-induced brain injury

作　　者：徐发林[1] 郭佳佳[1] 庄方莉 张彦华[1] 王彩红[1] 安蕊[1] 

机构地区：[1]郑州大学第三附属医院新生儿科,河南郑州450052 [2]许昌市中心医院新生儿科,河南许昌461000

出　　处：《中国当代儿科杂志》2014年第3期290-294,共5页Chinese Journal of Contemporary Pediatrics

基　　金：河南省教育厅自然科学研究计划项目(13A320664);河南省高等学校青年骨干教师资助计划(2012ggjs-015)

摘　　要：目的研究促红细胞生成素(EPO)对新生大鼠感染性脑损伤后神经细胞增生与凋亡的影响。方法 2日龄新生大鼠26只随机分为3组:对照组(腹腔注入等量生理盐水)、脂多糖(LPS)组(腹腔注入0.6 mg/kg LPS)及EPO干预组(腹腔注入0.6 mg/kg LPS+5 000 U/kg EPO),各组均连续注药5 d,同时腹腔注射5-溴脱氧尿嘧啶核苷(BrdU)(50 mg/kg,Qd,连续5 d),最后1次用药24 h后采用免疫组化方法检测脑组织海马齿状回颗粒下层BrdU和活化半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)的表达情况。结果 EPO干预组、LPS组脑组织海马齿状回单位面积内神经细胞数均显著低于对照组(P<0.05),但EPO干预组与LPS组比较差异无统计学意义。EPO干预组BrdU阳性表达较LPS组显著增多(51±9 vs 29±6),但仍较对照组(67±12)减少(P<0.05)。EPO干预组活化的Caspase-3阳性表达较LPS组显著减少(27.9±1.5 vs 34.0±1.3),但仍多于对照组(21.0±1.7),差异均有统计学意义(P<0.05)。结论 EPO可促进感染性新生大鼠脑损伤后海马区新生神经细胞的增生并减轻神经细胞的凋亡。Objective To investigate the effects of erythropoietin （EPO） on the neuronal proliferation and apoptosis in neonatal rats after infection-induced brain injury and the neuroprotective mechanism of EPO in neonatal rats with infection-induced brain injury. Methods Twenty-six two-day-old neonatal rats were randomly divided into 3 groups： control group （intraperitoneally given an equal volume of normal saline）, lipopolysaccharide （LPS） group （intraperitoneally given LPS 0.6 mg/kg）, and EPO group （intraperitoneally given LPS 0.6 mg/kg and EPO 5 000 U/kg）. These groups were injected with respective drugs for 5 consecutive days. Meanwhile, each group was intraperitoneally injected with 5-bromo-2＇-deoxyuridine （BrdU） （50 mg/kg） once a day for 5 consecutive days. The expression of BrdU and cleaved Caspase-3 in the hippocampal dentate gyms was detected by immunohistochemistry at 24 hours after the last injection. Results The number of neuronal cells in the hippocampal dentate gyms in the LPS and EPO groups was significantly greater than in the control group （P〈0.05）, but there was no significant difference between the LPS and EPO groups. The EPO group had a significantly higher number of BrdU-positive cells in the subgranular zone of hippocampal dentate gyrus than the LPS group （51±9 vs 29±6; P〈0.05）, but a significantly lower number of BrdU-positive cells than the control group （51±9 vs 67±12; P〈0.05）. The EPO group had a significantly lower number of cleaved Caspase-3- positive cells in the subgranular zone of hippocampal dentate gyrus than the LPS group （27.9±1.5 vs 34.0±1.3; P〈0.05）, but a significantly higher number of cleaved Caspase-3-positive cells than the control group （27.9±1.5 vs 21.0±1.7; P〈0.05）. Conclusions EPO can promote hippocampal neuronal proliferation and reduce neuronal apoptosis in neonatal rats after infection-induced brain injury.

关 键 词：促红细胞生成素 5-溴脱氧尿嘧啶核苷 活化半胱氨酸天冬氨酸蛋白酶-3 新生大鼠 

分 类 号：R722.1[医药卫生—儿科]