The Function And Mechanism Of DIP2A In Ischemia Stroke

Stroke,a serious common disease of the central nervous system with high disability,high mortality and high relapse,which was caused by sudden defect of cerebral blood flow.As the main pathological type of stroke,ischemic stroke produced about 80% of all stroke cases and afflicted the patients and their families with a huge mental and economic burden.At present,the outcome of clinical treatment of stroke was yet not as ideal as expected,which is mainly because the poor understanding of molecular mechanisms about this lethal illness.Therefore,Systematic research on molecular pathological mechanism of stroke,particularly ischemic stroke,was urgently required to promote the clinical prevention and treatment of the disease.DIP2A(Disco-interacting protein 2 homolog A)was a newly discovered cell membrane receptor and widely expressed in various tissues.In central nervous system,this protein was mainly distributed in neurons,which suggesting that DIP2 A may play an important role in the pathophysiology related to neurons.Accumulated studies have shown that DIP2 A acted as a receptor for glycoprotein FSTL1 and mediated the biological functions of FSTL1.Recently,there were some researches proved that FSTL1 played an important role in inhibiting apoptosis and activating autophagy induced by ischemia.Conversely,excessive apoptosis of neurons and hyperautophagsis would aggravate the damage to brain tissue brought by ischemic stroke.Therefore,we speculate that DIP2 A may play an important role in ischemic stroke.In this study,Dip2 a knockout mice were firstly used to establish ischemia-reperfusion model to study the role and mechanism of DIP2 A in ischemic stroke.Through TTC staining,Dip2 a gene-knockout was found to aggravate the damage of ischemic stroke on brain tissue and it also was shown by climbing plate experiments to aggravate the neurological impairment of ischemic stroke.The phosphorylation of AKT,a key regulator of apoptosis,was suppressed in Dip2 a Knockout mice,which consequently promotes ischemia-induce apoptosis.Meanwhile,Dip2 a knockout was indicated to promote cerebral ischemia-induce autophagy.This dissertation is of great significance for comprehensive and in-depth understanding of the pathological mechanism of ischemic stroke and the promotion of clinical research on cerebral ischemia.At the same time,it lays a theoretical foundation for the development of DIP2 A as a new molecular target for the treatment of stroke.