Abstract：Objective To investigate the protective effect of prostaglandin E1 (PGE-1) against brain injury induced by hyperoxia in neonatal rats and observe the changes in the expression of glucose-regulated protein 78 (GRP78) and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and to provide a theoretical basis for the clinical application of PGE-1 in the treatment of neonatal brain injury induced by hyperoxia. Methods Sixty neonatal Wistar rats were randomly divided into air control group, hyperoxic brain injury model group, and hyperoxic brain injury+PGE-1 group. All rats except those in the air control group were treated to establish a hyperoxic brain injury model. From the first day of modeling, the rats in the hyperoxia brain injury+PGE-1 group were intraperitoneally injected with PGE-1 2 μg/kg daily for 7 consecutive days, while the other two groups were treated with normal saline instead. The water content of brain tissue was measured; the pathological changes of brain tissue were evaluated by hematoxylin-eosin staining; the apoptosis of brain cells was assessed by nuclear staining combined with TUNEL staining; the protein expression of GRP78 and CHOP in brain tissue was measured by Western blot. Results The water content of brain tissue in the hyperoxic brain injury model group was significantly higher than that in the hyperoxic brain injury+PGE-1 group and air control group (P < 0.05); the water content of brain tissue in the hyperoxic brain injury+PGE-1 group was significantly higher than that in the air control group (P < 0.05). The pathological section of brain tissue showed inflammatory cell infiltration and mild cerebrovascular edema in the brain parenchyma in the hyperoxic brain injury model group; the periparenchymal inflammation and edema in the hyperoxic brain injury+PGE-1 group were milder than those in the hyperoxic brain injury model group. The apoptosis index of brain tissue in the hyperoxic brain injury model group was significantly higher than that in the hyperoxic brain injury+PGE-1 group and air control group (P < 0.05); the apoptosis index of brain tissue in the hyperoxic brain injury+PGE-1 group was significantly higher than that in the air control group (P < 0.05). The protein expression of GRP78 and CHOP in brain tissue was significantly higher in the hyperoxic brain injury model group than in the hyperoxic brain injury+PGE-1 group and air control group (P < 0.05); the protein expression of GRP78 and CHOP was significantly higher in the hyperoxic brain injury+PGE-1 group than in the air control group (P < 0.05). Conclusions PGE-1 has a protective effect against hyperoxia-induced brain injury in neonatal rats, which may be related to the inhibition of cell apoptosis by down-regulating the expression of GRP78 and CHOP.
YANG Shan,ZHANG You-Chen,LI Hui-Wen et al. Protective effect of prostaglandin E1 against brain injury induced by hyperoxia in neonatal rats[J]. CJCP, 2018, 20(3): 230-235.
Goren B, Cakir A, Sevinc C, et al. Uridine treatment protects against neonatal brain damage and long-term cognitive deficits caused by hyperoxia[J]. Brain Res, 2017,1676:57-68.
Rumajogee P, Bregman T, Miller SP, et al. Rodent hypoxia-ischemia models for cerebral palsy research:A systematic review[J]. Front Neurol, 2016, 7:57.
[10]
Semple BD, Blomgren K, Gimlin K, et al. Brain development in rodents and humans:Identifying benchmarks of maturation and vulnerability to injury across species[J]. Prog Neurobiol, 2013, 106-107:1-16.
[11]
Dorrell MI, Otani A, Aguilar E, et al. Adult bone marrow-derived stem cells use R-cadherin to target sites of neovascularization in the developing retina[J]. Blood, 2004, 103(9):3420-3427.
[12]
Kurul SH, Yiş U, Kumral A, et al. Protective effects of topiramate against hyperoxic brain injury in the developing brain[J]. Neuropediatrics, 2009, 40(1):22-27.
[13]
Benderro GF, Sun X, Kuang Y, et al. Decreased VEGF expression and microvascular density, but increased HIF-1 and 2α accumulation and EPO expression in chronic moderate hyperoxia in the mouse brain[J]. Brain Res, 2012, 1471:46-55.
[14]
Serdar M, Herz J, Kempe K, et al. Fingolimod protects against neonatal white matter damage and long-term cognitive deficits caused by hyperoxia[J]. Brain Behav Immun, 2016, 52:106-119.
[15]
Ritter J, Schmitz T, Chew LJ, et al. Neonatal hyperoxia exposure disrupts axon-oligodendrocyte integrity in the subcortical white matter[J]. J Neurosci, 2013, 33(21):8990-9002.
[16]
Chen X, Orriols M, Walther FJ, et al. Bone morphogenetic protein 9 protects against neonatal hyperoxia-induced impairment of alveolarization and pulmonary inflammation[J]. Front Physiol, 2017, 8:486.
[17]
Ogawa H, Kaira K, Takahashi K, et al. Prognostic role of BiP/GRP78 expression as ER stress in patients with gastric adenocarcinoma[J]. Cancer Biomark, 2017, 20(3):273-281.
[18]
Jiang Q, Chen S, Ren W, et al. Escherichia coli aggravates endoplasmic reticulum stress and triggers CHOP-dependent apoptosis in weaned pigs[J]. Amino Acids, 2017, 49(12):2073-2082.
[19]
Gezginci-Oktayoglu S, Orhan N, Bolkent S. Prostaglandin-E1 has a protective effect on renal ischemia/reperfusion-induced oxidative stress and inflammation mediated gastric damage in rats[J]. Int Immunopharmacol, 2016, 36:142-150.
