目的 通过重组人促红细胞生成素(recombinant erythropoietin ,rhEPO)对早产新生大鼠宫内感染脑损伤后神经胶质酸性蛋白和S-100β表达的影响,探讨其神经保护作用。方法 妊娠18 d孕鼠随机分为对照组、感染组和EPO干预组,对感染组及干预组分别给予LPS剂量0.45 mg/(kg·d)腹腔内注射,连用2 d,对照组按同样方法注射生理盐水,24 h后随机取部分孕鼠胎盘组织行HE染色观察其病理变化,余孕鼠继续怀孕至自然分娩,干预组新生鼠腹腔注射重组人促红细胞生成素5 000 U/(kg·d),连续注射3 d,部分待新生鼠6日龄大取其大脑,免疫组织化学法检测其大脑神经胶质酸性蛋白(the glial fibrillary acidic protein,GFAP)及酶联免疫方法检测血清中S-100β在宫内感染情况下及EPO干预后的不同表达变化。结果 与对照组比较,宫内感染及EPO干预组孕鼠胎盘组织HE染色后镜下观察均可见大量中性粒细胞浸润,血管充血、水肿等病理改变,与对照组比较,感染组、干预组GFAP的表达变化(对照组115.27±3.651;vs感染组105.68±3.189和干预组113.92±3.967)及S-100β结果(对照组0.32±0.05 vs感染组0.63±0.04,和干预组0.33±0.06),两组数据结果均显示感染组高于对照组及干预组,干预组及对照组差异无统计学意义。结论 宫内感染可使早产新生大鼠脑组织中GFAP及S-100β的表达均增加,而重组人促红细胞生成素降低宫内感染致脑损伤后神经胶质酸性蛋白和S-100β表达,保护脑组织。
Abstract
Objective To investigate the effects of recombinant erythropoietin(rhEPO) on expression of glial fibrillary acidic protein (EFAP) and S-100β in premature rat with intrauterine infection. Methods A total of 45 gestation 18 day pregnant rats were randomly divided into three groups,control group,received an intraperitoneal injection of normal saline,infection groups and intervention group were intraperitoneal injected with 0.45 mg/(kg·d) LPS continuting 2 days and the new rats in the intervention group were intraperitoneal injected with 5 000 U/(kg·d) rhEPO,continuting 3 days.Twenty-four hours after injection,part pregnant rats of each group were sacrificed.The pathological change of the placenta after HE staining was observed under light microscope.The glial fibrillary acidic protein (GFAP) and S-100β of the new 6 days rats' brains were examined by immunohistochemistry and enzyme linked immunosorbent assay(ELISA). Results Obvious pathological changes were observed in the placenta in the infection group and the intervention group.The GFAP on postnatal were 115.27±3.651 in control group,105.68±3.189 in infection group and 113.92±3.967 in intervention group and S-100β were (0.32±0.05 in control group 10.63±0.04 in infection group and 0.33±0.06 in intervention group.The GFAP and S-100β of infection group were significantly higher than those of control and intervention groups. Conclusions Intrauterine infection can increase the expression of GFAP and S-100βin the premature rats' cerebrum tisssue,rhEPO can decrease the expression of GFAP and S-100βand protect nervous system in neonatal rats with intrauterine infection made by LPS injection through abdominal cavity.
关键词
促红细胞生成素 /
新生大鼠 /
神经胶质酸性蛋白 /
S-100β
Key words
recombinant erythropoirth /
newborn premature rat /
the glial fibrillary acidic protein /
S-100β
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] 熊涛,屈艺,母得志,等.促红细胞生成素与新生儿脑损伤[J].中华儿科杂志,2011,49(10):756-760.
[2] Maleki Z,Bailis AJ,Argani CH,et al.Periventricular leukomalacia and placental histopathologic abnormalities[J].Obstet Gynecol,2009,114(5):1115-1120.
[3] Gantert M,Been JV,Gavilanes AW,et al.Chorioamnionitis:a multiorgan disease of the fetus[J].J Perinatol,2010,30(30S):21-30.
[4] Ennen CS,Huisman TA,Savage WJ,et al.Glial fibrillary acidic protein as a biomarker for neonatal hypoxic-ischemic encephalopathy treated with whole-body cooling[J].Am J Obstet Gynecol,2011,205(3):251-260.
[5] Kessler FH,Woody G,Portela LV,et al.Brain injury markers (S100βand NSE)in chronic cocaine dependents[J].Rev Bras Psiquiatr,2007,29(2):134-139.
[6] Bloomfield SM,McKinney J,Smith L,et al.Reliabiliti of S-100βin predicting severity of severity of central nervous system injury[J].Neurocrit Care,2007,6(2):121-138.
[7] 迟瑛娇,李晓捷,李莹,等.针刺对宫内感染致脑损伤仔鼠脑组织胶质纤维酸性蛋白表达的影响[J].实用儿科临床杂志,2007,22(15):1168-1171.
[8] Kellert BA,McPherson RJ,Juul SE.A comparison of high 2 dose recombinant erythropoietin treatment regimens in brain-injured neonatal rats[J].Pediatr Res,2007,61:451-455.
[9] 邵长荣,姜红.促红细胞生成素对缺氧缺血性脑损伤新生大鼠水通道蛋白4表达的影响[J].实用儿科临床杂志,2012,27(7):1075-1077.
[10] 许丽萍,任榕娜,朱少波,等.绒毛膜羊膜炎对早产儿脑损伤的影响[J].中国当代儿科杂志,2012,14(9):128-130.
[11] Iwai M,Stetler RA,Xing J,et al.Enhanced oligodendrogenesis and recovery of neurological function by erythropoietin after neonatal hypoxic/ischemic brain injury[J].Stroke,2010,41:1032-1037.
[12] Mazur M,Miller RH,Robinson S,et al.Postnatal erythropoietin treatment mitigates neural cell loss after systemic prenatal hypoxic-ischemic injury[J].J Neurosurg Pediatr,2010,6:206-221.
[13] Shen Y,Yu HM,Yuan TM,et al.Erythropoietin attenuates white metter damage proinflammatory cytokine and chemokine induction in developing rat brain after intra-uterine infection[J].J Neuropathology,2009,29(5):528-535.