Effects Of RhEPO On The Expression Of NMDA R1 MRNA And EPOR In Brain Tissue Of Neonatal Rats With Intrauterine Inflammation

Objective: To explore the neuroprotective effect and course treatment of recombinant human erythropoietin(rh EPO) on neonatal rats with white matter damage(WMD) after intrauterine infectionMethods: 12 wistar rats at 15 days of gestation were randomly divided into two groups:LPS group(n=9) and non-infection group(n=3). The infection group was established animal model of intrauterine infection by intraperitoneal injection of lipopolysaccharide(LPS) while the non-infection group received the same volume of saline injection instead.Pathological changes of placenta(n=6) and brain tissue(n=10)selected randomly from fetal rats were observed by hematoxylin eosin(HE) staining. randomly selected 32 newborn rats in the control group as the premature birth control group; selected 64 newborn rats in the infection group and randomly divided into EPO treatment group(n=32) and infection control group(n=32). Regarding EPO treatment group, conducted intraperitoneal injection of rh EPO(5000IU/Kg) promptly after the birth. Regarding premature control group and infection control group, conducted intraperitoneal injection of equivalent saline solution simultaneously. As for newborn rats in three groups, took 10 premature rats on0 h,3rd,7rd and 14 th day after their birth respectively and took out brain by perfusing formaldehyde. Level of NMDAR1 m RNA was detected by RT-PCR and the level of EPOR in tissue was detected by ELISA.Results:1.The general situation: There were two pregnant rats died after LPS injection. The mortality was 18.2%. Six pregnant rats in infection group all happened delivery in their 19.0-20.5 days. While pregnant rate in infection group labored newborn rats in 22.0-22.5 days. 2.The placenta of pregnant rats in the infection group featured congestion of blood vessel and edema with a lot of visible neutrophile granulocytes infiltrated. Loose structure of the white matter of prematurerats was obvious and the neurons were lack of differentiation with small cell volume、small nucleus and little neuronal process. Weaking staining and focal rarefaction of the periventricular white matter of the infection group were observed. Clear staining and normal structure of periventricular white matter were show in non-infection group.3.The level of EPOR in brain tissue was detected by ELISA :in infection controlgroup and EPO treatment group, EPOR level in brain tissue of rats of 3d and 7d old was remarkably increased compared to that in the premature control group.There was statistical significance in difference among each(P<0.05);The concentrations of EPOR in the rh EPO treated group were significantly higher than that in the control group at third days, and the high expression levels remained at 14 th days, It,s significant differences compared with the infection control group(P<0.05). 4.The level of NMDA R1 m RNA in brain tissue was detected by RT-PCR:n infection control group and EPO treatment group, EPOR level in brain tissue of rats of 0d 、3d、7d old was remarkably increased compared to that in the premature control group.There was statistical significance in difference among each(P<0.05);Conclusion:1.By intraperitoneal injection of LPS in pregnant rats, we can successfully conduct the model of preterm brain injury. 2.The.NMDA was overactivatio in nneonatal rats with white matter damage white matter caused by Intrauterine inflammation.Rh EPO can inhibit the excitatory toxic effect of NMDA mediated amino acids, and promote the expression of EPOR, so as to reduce the damage of brain tissue caused by intrauterine inflammation. 3.EPO is superior to be administered at early time than at later time.The 14 day course of treatment is currently the best course of treatment.