The Effects Of Apelin-36 On The Expression Of MBP And NG2 In The White Matter Of The Neonatal Rat Model With Periventricular Leukomalacia

Objective:To investigate the neuroprotective effect of apelin-36 by testing the expression of myelin basic protein(MBP)and neuron-glial antigen2(NG2)in the white matter of the neonatal rat model with periventricular leukomalacia.Methods:The animal models of 3 day old SD rats with periventricular leukomalacia(PVL) were made by the ligation of the left common carotid artery and then in halation of mixed gas of 92%N2+8%O2 for 1 hour, the rats with PVL were randomly divided into the model group of PVL and the apelin trial group,and the sham operation group that was established by only separating the left common carotid artery without ligation and hypoxia.The pathologic changes of brain were observed by optical microscope on day 7,day 14 and day 21;The expression of MBP and NG2 in periventricular white matter were examined with immunohistochemical staining and image quantitative analysis.The remained eight rats in each group at day 30 were tested long-term memory through Morris water maze.Results:1.Pathologic changes of brain tissues in the three groups of neonatal SD rats:The pathological lesion mainly occured in periventricular white matter,hippocampus, internal capsule,callosal convolution and external capsule in both the model group of PVL and the apelin trial group;The injury in subcortica was mild.At day 7 cell edema,necrosis and disordered arrangement in the hippocampus were discovered,and loose,edema,porous and malacotic structure and even liquefactive necrosis in periventricular white matter were observed; At day 14,the left side of the lateral ventricle enlarged at different degree;the pore structure decreased; malacia and liquefactive necrosis in periventricular white matter were markedly reduced;the glial cells and nerve fibers hyperplasia were also detected;At day 21 the formation of glial scar and nerve fibers hyperplasia were observed in part of periventricular white matter; encephalomalacia and liquefactive necrosis further reduced;but brain tissues still had a malacia and irregular structure; pathologic changes of brain tissue in the apelin-36 trial group were significantly ameliorated.There were no morphological and structure anomalies in the brain tissue of the sham group through HE staining sections at day 7,day 14 and day21.2.Immunohistochemical staining in the periventricular white matter2.1 The expression of MBP in the three groups of neonatal SD rats in the periventricular white matterAt day 7,day 14 and day21 the expression of MBP in periventricular white matter was increasing gradually with the increase of age;At the same time-point,the expression of MBP in the sham group was maximum,next was apelin trial group,and the expression of MBP in the model group of PVL was minimum.Analysis of variance showed that there was significant difference in expression level of MBP among the three groups(P<0.05).2.2 The expression of NG2 in the three groups of neonatal SD rats in the periventricular white matter:At day 7,day 14 and day21 the expression of NG2 in periventricular white matter was decreasing by degrees with the increase of age;At the same time-point,the sham group showed a minimum of NG2;next was apelin-36 trial group, and the model group of PVL expressed maximum of NG2;by the analysis of variance there was significant difference in expression level of NG2 in all the three groups(P<0.05).3.Morris water mazeThe ability of learning and memory was detected through Morris water maze at day30;(1) escaping latency of the sham group was shortest,then was the apelin trial group,and escaping latency of the model group of PVL was longest;Analysis of variance indicated that there was significant difference of escaping latency in all groups at the same time-point(P<0.05);(2)The frequency of crossing the platform of the sham group was most,next was the apelin-36 trial group;and that in the model group of PVL was least.There was significant difference of the number of crossing the platform among the three groups.(P<0.05).Conclusion:1.Manifestation of pathologic change in the brain indicated successful establishment of the PVL model by ligaturing the left common carotid artery of the day 3 rats and following inhalation of mixed gas of 92%N2+8%O2 for 1 hour.2.Apelin-36 could relieve cerebral loose,edema,reduce malacia and liquefactive necrosis and alleviated cerebral ventricle expansion; It suggest that apelin-36 may play important role in the neuroprotective effect of the PVL models of rats.3.Apelin-36 could increase the expression level of MBP and reduce NG2 expression level in periventricular white matter of the neonatal rat with PVL.It indicated that apelin-36 may facilitate the differentiation and maturation of oligodendrocyte.4.Apelin-36 shorten escaping latency and increased the frequency of crossing the platform;All this demonstrated that apelin-36 significantly improved the long-term learning and memory ability of the neonatal rat model with periventricular leukomalacia.