Effects Of Adenosine Pretreatment On Blood Brain Barrier And AQP₄ Expression In Rats With Acute Cerebral Infarction

BackgroundIschemic stroke is a serious social problem,which is harmful to the health of patients and tends to be younger.Brain edema is the most common pathological phenomenon after cerebral ischemia-reperfusion?IR?.Whether many critical patients can survive or not depends on whether they can pass the brain edema stage.Most of brain edema is due to the damage of blood brain barrier?BBB?,so the key to reduce brain edema is to reduce the damage of BBB.There are many kinds of endogenous nucleosides in human body.Adenosine?ADO?is one of them.It is widely distributed in tissue cells and has physiological effects on many systems of the body.It has been shown that adenosine pretreatment has neuroprotective effect,but it has not been reported on the effect of BBB function.So it is very meaningful to explore the effect of adenosine pretreatment on brain tissue from the perspective of BBB,and provide more theoretical basis for adenosine pretreatment in the treatment of ischemic cerebrovascular disease.ObjectiveBy observing the effect of adenosine pretreatment on BBB permeability and AQP₄expression in the brain around the infarct area,the protective effect of adenosine pretreatment on brain and its possible mechanism were discussed from the perspective of BBB.Method?1?120 healthy male SD?Sprague Dewley?rats were randomly divided into sham operated group?F Group?,model group?IR group?,adenosine pretreatment group?AP group?,40 rats in each group.According to the time of killing animals,each group was divided into four subgroups:6h,24h,48h and 72h?F6,24,48,72h,ir6,24,48,72h,AP6,24,48,72h?.There were 10 animals in each subgroups,5 of which were randomly used to measure EB exudation,the remaining 5 were used to prepare brain slices,measure AQP4expression and HE.Adenosine injection 1.5mg/kg?diluted to 2ml of normal saline?was intraperitoneally injected into AP group three days before modeling,once a day for three consecutive days;F and IR groups were intraperitoneally injected 2ml of normal saline three days before operation,once a day for three times.?2?The rats in group F were exposed to the left common carotid artery without ligation.The middle cerebral artery occlusion?MCAO?model was made in group IR and group AP respectively.The thrombus line was pulled out for 1cm 2 hours after the model was made successfully.The neurological symptom score was used to test whether the model was made successfully,and the brain was cut off.HE was used to observe the changes of brain histomorphology;Evans blue?EB?permeability was used to analyze the changes of BBB permeability;The expression of AQP₄ protein was detected by immunohistochemistry.Result?1?Pathological changes of brain tissue around the infarct area:with the prolongation of CIR,edema,nuclear pyknosis,degeneration of nerve cells,necrosis and proliferation of glial cells in the brain tissue around the infarct area became more and more serious in the rest groups except F group;compared with IR group,the pathological changes of brain tissue around the infarct area were significantly reduced in AP group at different time points of reperfusion.?2?BBB permeability:compared with group F,EB exudation in IR group and AP group was significantly more,the difference was statistically significant?P<0.05?;with the prolongation of CIR time,EB exudation in IR group and AP group increased gradually,reached the peak value at 48 hours after reperfusion,and began to decline but still higher than the normal level;compared with IR group,EB exudation in brain tissue around infarct area was clear at different time points after reperfusion in AP group,the difference was statistically significant?P<0.05?.?3?AQP₄ protein expression:compared with F group,the expression of AQP₄ in IR group and AP group was significantly higher?P<0.05?;With the prolongation of CIR time,AQP4 expression increased gradually in IR group and AP group,peaked at 48h,and remained at the peak at 72h after reperfusion;Compared with IR group,the expression of AQP₄ in the brain around the infarct area decreased significantly at different time points of reperfusion?P<0.05?.?4?There was a significant positive correlation between the change of BBB permeability and the change of AQP4 expression in the brain tissue around the infarcted area at each time point after cerebral ischemia-reperfusion injury?r=0.898,P<0.001?.Conclusion?1?Adenosine pretreatment can improve the malignant pathomorphological changes and BBB permeability of the brain around the infarcted area.?2?Adenosine pretreatment can reduce the expression of AQP₄ in the brain around the infarcted area of rats.?3?Adenosine pretreatment can improve the permeability of BBB by regulating the expression of AQP₄,so as to reduce brain edema and protect brain tissue.