Abstract：Objective To investigate the role of miRNA-210 in hypoxic-ischemic brain edema in neonatal rats. Methods A total of 80 neonatal rats were randomly divided into control group, normal saline group, miRNA-210 expression inhibition group, and miRNA-210 overexpression group, with 20 rats in each group. Each group was randomly divided into sham-operation group and hypoxia-ischemia (HI) group, with 10 rats in each group. The neonatal rats in the HI group were treated with ligation of the left common carotid artery and then put in a hypoxia cabin with mixed gas of 8% O2 and 92% N2 for 2 hours; those in the sham-operation group were treated with isolation of the left common carotid artery only, without ligation or hypoxia treatment. After HI or sham-operation, the rats in the normal saline group, miRNA-210 expression inhibition group, and miRNA-210 overexpression group were intracranially injected with normal saline (2.5 mg/kg), miRNA-210 inhibitor (2.5 mg/kg), and miRNA-210 mimic (2.5 mg/kg) respectively. No treatment was given to the rats in the control group. The rats were sacrificed three days later, and the left brain tissue was harvested. Fluorescent quantitative PCR was used to measure the expression of miRNA-210; the dry-wet weight method was used to measure the water content of brain tissue; hematoxylin and eosin staining was used to observe the histomorphological changes in the brain. Results The HI groups showed significant reductions in the expression of miRNA-210 and significant increases in the water content of brain tissue compared with the corresponding sham-operation groups (P < 0.05). Compared with the normal saline HI group, the miRNA-210 expression inhibition HI group showed a significant reduction in the expression of miRNA-210 and a significant increase in the water content of brain tissue (P < 0.05), and the miRNA-210 overexpression HI group showed a significant increase in the expression of miRNA-210 and a significant reduction in the water content of brain tissue (P < 0.05). The results of hematoxylin and eosin staining suggested that the miRNA-210 expression inhibition HI group showed marked edema, and the miRNA-210 overexpression HI group showed a significant improvement in edema. Conclusions Neonatal rats show down-regulated expression of miRNA-210 after HI, suggesting that miRNA-210 may be involved in the development and progression of hypoxic-ischemic brain edema in neonatal rats.
Ivan M,Harris AL,Martelli F,et al.Hypoxia response and microRNAs:no longer two separate worlds[J].J Cell Mol Med,2008,12(5A):1426-1431.
[2]
Camps C,Buffa FM,Colella S,et al.hsa-miR-210 is induced by hypoxia and is an independent prognostic factor in breast cancer[J].Clin Cancer Res,2008,14(5):1340-1348.
[3]
Qiu J,Zhou XY,Zhou XG,et al.Neuroprotective effects of microRNA-210 on hypoxic-ischemic encephalopathy[J].Biomed Res Int,2013,2013:350419.
[4]
Qiu J,Zhou XY,Zhou XG,et al.MicroRNA-210 knockdown contributes to apoptosis caused by oxygen glucose deprivation in PC12 cells[J].Mol Med Rep,2015,11(1):719-723.
[5]
Qiu J,Zhou XY,Zhou XG,et al.Neuroprotective effects of microRNA-210 against oxygen-glucose deprivation through inhibition of apoptosis in PC12 cells[J].Mol Med Rep,2013,7(6):1955-1959.
[6]
Rice JE 3rd,Vannucci RC,Brierley JB.The influence of immaturity on hypoxic-ischemic brain damage in the rat[J].Ann Neurol,1981,9(2):131-141.
[7]
Fasanaro P,D'Alessandra Y,Di Stefano V,et al.MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3[J].J Biol Chem,2008,283(23):15878-15883.
[8]
Giannakakis A,Sandaltzopoulos R,Greshock J,et al.miR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer[J].Cancer Biol Ther,2008,7(2):255-264.
[9]
Jeyaseelan K,Lim KY,Armugam A.MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion[J].Stroke,2008,39(3):959-966.
[10]
van den Tweel ER,Kavelaars A,Lombardi MS,et al.Bilateral molecular changes in a neonatal rat model of unilateral hypoxic-ischemic brain damage[J].Pediatr Res,2006,59(3):434-439.
[11]
Mu D,Jiang X,Sheldon RA,et al.Regulation of hypoxia-inducible factor 1alpha and induction of vascular endothelial growth factor in a rat neonatal stroke model[J].Neurobiol Dis,2003,14(3):524-534.
[12]
Liu DZ,Tian Y,Ander BP,et al.Brain and blood microRNA expression profiling of ischemic stroke,intracerebral hemorrhage,and kainate seizures[J].J Cereb Blood Flow Metab,2010,30(1):92-101.
[13]
Zeng L,Liu J,Wang Y,et al.MicroRNA-210 as a novel blood biomarker in acute cerebral ischemia[J].Front Biosci (Elite Ed),2011,3:1265-1272.
