目的：观察促红细胞生成素(erythropoietin，EPO)及其受体(EPOR)在宫内窘迫大鼠生后脑组织的动态表达规律,并探讨其意义。方法：采用结扎足月妊娠待产时母鼠双侧子宫动脉10 min 后行剖宫产制作新生大鼠宫内窘迫的模型作为实验组,研究新生大鼠生后不同时间点（0 h、2 h、6 h、12 h、24 h、48 h、3 d和7 d）脑组织EPO及EPOR的动态表达情况,并同时检测血清EPO的水平。未结扎双侧子宫动脉的剖宫产新生大鼠作为对照组。结果：与对照组相比，实验组EPO蛋白和mRNA的表达在2 h、6 h、12 h等3个时间点明显增强（均P<0.05）；EPOR蛋白和mRNA的表达在2 h、6 h、12 h、24 h、48 h、3 d等6个时间点均明显增加（均P<0.05）。实验组血清EPO水平在生后2 h高于对照组,差异有统计学意义（t=2.52,P=0.02）。结论：宫内窘迫新生大鼠生后脑组织EPO和EPOR在短期内迅速增加，而且EPOR高表达持续时间较EPO长。这一发现为外源性EPO治疗胎儿宫内窘迫致新生儿脑损伤提供了有力依据。
Abstract
OBJECTIVE: To study the expression of erythropoietin (EPO) and its receptor (EPOR) in the brain of newborn rats suffering fetal distress. METHODS: A model of fetal distress was prepared by ligating bilateral uterine arteries of the rats with full-term pregnancy for 10 minutes before cesarean sections. The expression levels of EPO and EPOR in the brain of newborn rats were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot at 0, 2, 6, 12, 24, 48, 72 hrs and 7 days after birth. Serum EPO levels were measured using ELISA simultaneously. The newborn rats born by cesarean sections which were not subjected to uterine artery ligation were used as the control group. RESULTS: The expression of EPO protein and mRNA in brain tissues in the fetal distress group increased significantly compared with the control group 2, 6 and 12 hrs after birth (P<0.05). The expression of EPOR protein and mRNA in brain tissues in the fetal distress group increased significantly compared with the control group 2, 6, 12, 24 and 48 hrs, and 3 days after birth (P<0.05). Serum EPO levels in the fetal distress group were significantly higher than in the control group 2 hrs after birth. CONCLUSIONS: The EPO and EPOR levels in the brain increase quickly after birth in newborn rats suffering from fetal distress. The EPOR is high expressed for a longer time than EPO. This can provide a basis for the treatment of neonatal brain damage induced by fetal distress by exogenous EPO.
关键词
促红细胞生成素 /
促红细胞生成素受体 /
脑 /
宫内窘迫 /
新生大鼠
Key words
Erythropoietin /
Erythropoietin receptor /
Brain /
Fetal distress /
Newborn rats
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
［1］Ribatti D, Vacca A, Roccaro AM, Crivellato E, Presta M. Erythropoietin as an anggenic factor［J］. Eur J Clin Invest, 2003, 33(10): 891-896.
［2］丁璐,吴本清,黄进洁,刘智屏,陈丽.促红细胞生成素对新生大鼠高氧肺损伤细胞凋亡的影响［J］.中国当代儿科杂志, 2010, 12(7):576-579.
［3］陈晓晴,许华,罗小平,黎萍.促红细胞生成素对缺氧缺血性脑损伤新生大鼠脑组织存活素表达及神经细胞凋亡的影响［J］.实用儿科临床杂志，2011，26（2）:91-93.
［4］van der Kooij MA, Groenendaal F, Kavelaars A, Heijnen CJ, van Bel F. Combination of deferoxamine and erythropoietin: therapy for hypoxia-ischemiainduced brain injury in the neonatal rat?［J］.Neurosci Lett,2009,451(2):109-113.
［5］薄涛,严超英,霍淑芳,李巍.结扎孕鼠双侧子宫动脉复制围产期缺氧缺血性脑损伤动物模型［J］.中风与神经疾病杂志,2001,18(1):18-19.
［6］Dereski MO, Chopp M, Knight RA, Rodolosi LC, Garcia JH. The heterogeneous temporal evolution of focal ischemic neuronal damage in the rat［J］.Acta Neuropathol,1993,85(3):327-333.
［7］Marzo F, Lavorgna A, Coluzzi G, Santucci E, Tarantino F, Rio T, et al. Erythropoietin in heart and vessels: focus on transcription and signalling pathways［J］.J Thromb Thmmbolysis, 2008, 26(3):183-187.
［8］Sasaki R, Masuda S, Nagao M. Erythropoietin: multiple physiological functions and regulation of biosynthesis［J］.Biosci Biotechnol Biochem,2000,64(9):1775-1793.
［9］Parsa CJ, Matsumoto A, Kim J, Riel RU, Pascal LS, Walton GB, et al. A novel protective effect of erythropoietin in the infarcted heart［J］. J Clin Invest, 2003, 112(7): 999-1007.
［10］Teramo KA, Widness JA. Increased fetal plasma and amniotic fluid erythropoietin concentrations: markers of intrauterine hypoxia［J］. Neonatology, 2009, 95(2): 105-106.
［11］Kumral A, Genc S, Ozer E, Yilmaz O, Gokmen N, Koroglu TF, et al. Erythropoietin downregulates bax and DP5 proapoptotic gene expression in neonatal hypoxicischemic brain injury［J］. Biol Neonate, 2006, 89(3): 205-210.
［12］Genc S, Koroglu TF, Genc K. Erythropoletin and the nervous system［J］. Brain Res, 2004, 1000(1-2): 19-31.
［13］Sun Y, Calvert JW, Zhang JH. Neonatal hypoxia/ischemia is associated with decreased inflammatory mediators after erythropoietin administration［J］. Stroke, 2005, 36(8): 1672-1678.
［14］Kumral A, Uysal N, Tugyan K, Sonmez A, Yilmaz O, Gokmen N, et al. Erythropoietin improves long-term spatial memory deficits and brain injury following neonatal hypoxiaischemia in rats［J］.Behav Brain Res, 2004, 153(1): 77-86.
［15］Uzüm G, Sarper Diler A, Bahcekapili N, Ziya Ziylan Y. Erythropoietin prevents the increase in blood-brain barrier permeability during pentylentetrazol induced seizures［J］. Life Sci, 2006, 78(22): 2571-2576.
［16］Fauchère JC, Dame C, Vonthein R, Koller B, Arri S, Wolf M, et al. An approach to using recombinant erythropoietin for neuroprotection in very preterm infants［J］.Pediatrics,2008,122(2):375-382.
［17］Xiong Y, Mahmood A, Qu C, Kazmi H, Zhang ZG, Noguchi CT, et al. Erythropoietin improves histological and functional outcomes after traumatic brain injury in mice in the absence of the neural erythropoietin receptor［J］. J Neurotrauma, 2010, 27(1): 205-215.
PDF(1525 KB)
