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.
ZHANG Zhi-Min,TIAN Zhao-Fang,LI Yu-Hong et al. Expression of erythropoietin and its receptor in the brain of newborn rats suffering from fetal distress[J]. CJCP, 2011, 13(11): 912-916.
[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.
[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.