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The Effect Of Human Albumin On Permeability Of Blood Brain Barrier(BBB) In Brain Ischemic-reperfusion(I/R)Rats

Posted on:2018-02-27Degree:MasterType:Thesis
Country:ChinaCandidate:Y Q ZhangFull Text:PDF
GTID:2334330518467385Subject:Emergency medicine
Abstract/Summary:PDF Full Text Request
Ischemic stroke is the commonest neurological disease and ischemia can injure the brain tissue directly.Meanwhile ischemic reperfusion could give the brain second injury and long-last injury.Nowadays,many neuroprotective agents are being studied by scientists,albumin is one of them,some study showed that the albumin could significantly reduce the lesion and edema lead by brain IR,however some RCTs and basic studies show a different outcome.So,however it's important to reconfirm the effects of albumin on brain IR injury.Objective:To determine the effect of high dose albumin on permeability of blood brain barrier(BBB)in brain ischemic-reperfusion(IR)rats in and further explore its possible mechanisms.Methods:Brain ischemic reperfusion rat model by middle cerebral artery occlusion(MCAO).Medicine treatment was given by caudal vein injection after 2 hours of occlusion.36 healthy male SD rats,were then randomly divided into 6 groups(n=6 in each):sham-operation group(Group Sham:operation without ischemia),normal saline group(Group NS:NS injection 5 ml/kg)and albumin group(Group Alb:25%Alb injection 1.25 g/kg).After 6 h and 24 h each at the end of reperfusion,serum concentration of S100B was examined by the ELISA kit and Evans blue in brain tissue was detected by spectrophotometer.Rats were measured by Zea-Longa score separately.The expressions of ZO-1,Occludin,AQP4 were examined by Western blot and immunohistochemistry.All data was analyzed by one-way analysis of variance(ANOVA),The intergroup comparisons were analyzed by the least-significant-difference(LSD)test by using SPSS version 17.0 software.Differences were considered statistically significance if P<0.05.Results:The serum concentration of S100B in group NS 6 h is significantly lower than that in group Alb at 6 h(196.67±20.11 vs.160.04±14.00,P=0.000),and was the same in 24 h(2.45±0.07 vs.2.23±0.07,P=0.000).Furthermore,concentration of Evans blue in brain tissue of group Alb was significantly higher than that is group NS in both 6 h(0.97±0.08 vs.0.74±0.06,P=0.000)and 24 h(2.45±0.07 vs.2.23±0.07,P=0.000).Zea-Longa score significantly increased for both group NS and group Alb in 6 h and 24 h(P=0.000).However,there was no significant difference in 6 h and 24 h(p=1.000)between group Alb and group NS.After 6 h and 24 h treatment,there were no significant differences between group NS and Alb in IR lesion(25.69±1.19-vs.28.51±0.47,P=0.433)and(27.31±0.15 vs.29.21±0.95,P=0.107).But the rADC calculated by software from DTI sequence showed significant differences between group Alb and NS both in 6 h(0.83±0.05 vs.0.72±0.06,P=0.000)and 24 h(0.67±0.07 vs.0.58±0.01,P =0.001).Examed by transmission electron microscope(TEM),there were no difference between group NS and Alb both in 6 h and 24 h in micromorphology.In respect of AQP4 expression in brain tissue,group Alb expressed higher than group NS in both 6h(P<0.05)and 24 h(P<0.05);As for expression of ZO-l,Occludin,compared with group NS,there was no significant difference in 6 h(P>0.05),expression of both protein were significantly lower in group Alb at 24 h(P<0.05).Conclusions:In this study,albumin contribute slightly to improving neuro-defects in IR rats and can not reduce the lesion of IR.It can also aggravate the injury of IR,which increases brain edema by increase the permeability in BBB.The mechanism may be related to reduce ZO-l,Occludin expression and and increase AQP4 expression in brain tissue.
Keywords/Search Tags:Albumin, BBB, IR, Nuro-defect, AQP4, Tight junction proteins
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