| BackgroundThe incidence of ischemic cerebrovascular disease increased year by year,causing great harm to human health and the quality of survival,and thus the study of the disease has become a hot direction to constantly seek new therapeutic targets.To save the ischemic penumbra as soon as possible become one of the important point of the research on ischemic cerebrovascular disease.In the past studies,ABT-702 as a novel nonnucleoside adenosine kinase inhibitor(AKI)can enhance the levels of adenosine(Ado)in vivo and the protective effect proved in a variety of diseases.However,the role of ABT-702 in ischemic cerebrovascular disease has not been reported.ObjectiveTo explore the expression of adenosine and Beclin1 protein in rat brain in rat model of ischemic reperfusion injury after using ABT-702,and to further confirm that ABT-702 has a protective effect on the brain Role.Provide the data basis for the research and application of ischemic cerebrovascular disease.Method84 male rats were randomly divided into control group,sham operation group,model group and ABT-702 group,21 rats in each group.All rats received neurological deficit score after reperfusion.We select 6 rats to detect the infarct size according to TTC staining in each group.Then we select 9 rats and divided into three subgroups randomly to detect the adenosine content of brain tissue by High Performance Liquid Chromatography(HPLC)at different time points in each group.Six rats were randomly selected to detect the Beclin1 expression by RT-PCR in each group at last.Result1.The neurological deficit function score of ABT-702 group lower than the modelgroup.The score of both control group and sham operation group were 0 according to Zea Longa.Both of model group and ABT-702 group have the syndrome of neurological deficits.But the scores of ABT-702 neurological deficits were significantly lower than that of the model group(P<0.05).2.The infarct volume of ABT-702 group was significantly lower than that of model group.There was no infarct area after TTC staining in the control group and the sham operation group.But the model group and the ABT-702 group showed a large infarct area(white after TTC staining).However,the infarct volume of ABT-702 group was significantly small compared with the model group(P<0.05).3.The changes of adenosine content in rat brain were detected by HPLC.The levels of adenosine in brain tissue were detected by HPLC at different time points(2h,6h,12h)after reperfusion.The results suggest that the presence of adenosine can be detected at each time point in each group.The different of adenosine level in the control group and sham group were insignificantly.Compared with the control group and sham operation group,the levels of adenosine in the model group and the ABT-702 group were higher at 2h and 6h after reperfusion.The adenosine levels of ABT-702 group were higher than the model group in the reperfusion period.However,the level of adenosine in ABT-702 group was lower than that at 2h and 6h after reperfusion at 12 h.4.The expression of Beclin1 mRNA in brain tissueThe expression of Beclin1 mRNA were find in each group after 6 hours of reperfusion.But the level of Beclin1 mRNA in the model group was higher than that in the control group and the sham operation group.The expression of Beclin1 in ABT-702 group was significantly higher than that in the other three groups.Conclusion1.ABT-702 in rats with ischemia-reperfusion injury has a protective effect.It reducethe neurological damage and the infarct size of the brain tissue.2.The content of adenosine in brain tissue was significantly increased after applying of ABT-702.And the content of adenosine at 6 hours after reperfusion was the highest.3.ABT-702 increased the expression level of autophagy related protein,Beclin1,in rat model of ischemia-reperfusion,which may be one of the protective effect mechanisms of ABT-702 in rats with cerebral ischemia reperfusion injury(CIRI). |
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