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. 2020 Aug;27(8):2129-2133.
doi: 10.1016/j.sjbs.2020.05.040. Epub 2020 Jun 1.

Therapeutic effect of erythropoietin on brain injury in premature mice with intrauterine infection

Hongxue Liu  1 , Muling Zhang  1 , Xiao Han  2
Affiliations

Therapeutic effect of erythropoietin on brain injury in premature mice with intrauterine infection

Hongxue Liu et al. Saudi J Biol Sci. 2020 Aug.

Abstract

Objective: The objective of this study is to explore the protective effect of erythropoietin (EPO) on brain injury induced by intrauterine infection in premature infants and its related mechanism, so as to provide reference for clinical medication.

Methods: Intrauterine infection model is established by injecting lipopolysaccharide into pregnant mice, and HE staining of mouse placenta is used to judge whether the model of intrauterine infection is successful or not. Fifteen female rats are successfully pregnant and divided into intrauterine infection group (10 rats) and control group (5 rats). The mice in the intrauterine infection group are intraperitoneally injected with lipopolysaccharide (LPS) at a dose of 0.3 mg/kg. After delivery, 16 newborn mice in the control group are randomly selected as blank control group. 32 newborn mice in the intrauterine infection group are selected as model group, and then divided into infection group and EPO treatment group, 16 mice in each group. After birth, mice in the blank control group are intraperitoneally injected with 0.2 mL saline daily. The infected mice are intraperitoneally injected with 0.2 mL saline daily. The mice in the EPO treatment group are intraperitoneally injected with recombinant human erythropoietin (rhEPO) 5000 IU/kg daily. HE staining results, EPOR protein and NMDAR1 mRNA expression in brain tissue of three groups of neonatal mice were compared.

Results: Firstly, the blood vessels of the mice in the intrauterine infection group are markedly hyperemic and edematous, and the infiltration of neutrophils is increased. The white matter structure of the neonatal mice in the intrauterine infection group is loose and stained lightly. The nerve fibers in the brain are different in thickness and disordered in arrangement. The nucleus is small and dark stained. The number of glial cells in brain tissue increases significantly. Secondly, the EPOR protein expression and physiological level of neonatal mice in intrauterine infection group increase significantly at 3, 7 and 14 days after birth. Compared with the blank control group, the difference is statistically significant (P < 0.05). On the 3rd day after birth, the expression level of EPOR protein in the EPO treated group is significantly higher than that in the intrauterine infection group (P < 0.05). Thirdly, the expression level of NMDA R1mRNA in brain tissue of neonatal mice at birth, on the 3rd and 7th day after EPO treatment is significantly lower than that of intrauterine infection group (P < 0.05).

Conclusion: EPO can promote the proliferation and differentiation of brain endogenous neural stem cells, and has a certain therapeutic effect on brain injury of premature mice caused by intrauterine infection.

Keywords: Brain hypoxia; Brain injury; Erythropoietin; Intrauterine infection; Premature mice.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
HE staining in pathological examination of placenta of mice in intrauterine infection group and normal group (* 400).
Fig. 2
Fig. 2
HE staining in brain tissue of neonatal mice in intrauterine infection group and normal group (* 400).
Fig. 3
Fig. 3
Trends of EPOR protein levels after birth in three groups of mice.
Fig. 4
Fig. 4
Trends of NMDAR1 expression in three groups of mice after birth.
See this image and copyright information in PMC

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