| Background:Sestrin2(Sesn2)is a stress-responsive protein that has been shown to have neuroprotective properties in certain neurodegenerative diseases.However,the impact of Sesn2 on clinical outcomes of stroke remains unclear.The nuclear factor-erythrocyte 2-related factor 2/heme oxygenase-1(Nrf2/HO-1)pathway is critical in the process of angiogenesis and contributes to the reduction of cerebral ischemic injury.However,its specific brain protection mechanism is still unclear.Objective:To investigate whether Sesn2 can attenuate cerebral ischemic injury by activating Nrf2/HO-1 pathway to promote vascular regeneration after cerebral ischemia.Methods:(1)Two weeks before rat modeling,Sesn2 overexpressing adenoassociated virus(AAV-Sesn2)was injected into the right ventricle(5 ul,10ug/ul)and Nrf2 interfering with lentivirus(LV-Nrf2)into the rightventricle(5 ul,2 ug / ul),and then the rat model of focal cerebral ischemic injury was prepared by photochemical embolization.(2)The protein expression levels of Sesn2,nuclear Nrf2,HO-1 and VEGF were detected by Western blot;the volume of cerebral infarction was detected by TTC staining;the neurological deficit was assessed by mNSS scoring and adhesive removal test.(3)Detection of lumen formation by CD31 immunofluorescence double staining.The number of neovascular endothelial cells was detected by DCX immunofluorescence double staining,which indirectly reflected the regeneration of blood vessels.Results:(1)After cerebral ischemic injury,the protein expression of Sesn2 is increased in the cerebral cortex;at the same time,the expression level of nuclear Nrf2 is up-regulated,and the protein expression of angiogenesisrelated proteins HO-1 and VEGF is increased.(2)After overexpressing Sesn2 with adeno-associated virus,the expression level of Nrf2 is up-regulated,and the protein expression levels of angiogenesis-related proteins HO-1 and VEGF are up-regulated.In addition,overexpression of Sesn2 significantly reduced the volume of cerebral infarction,reduced neurological function score and binder removal time,increased microvascular lumen formation,and increased vascular endothelial cells.(3)After using lentivirus to interfere with the expression of Nrf2,the protein expression levels of angiogenesis-related proteins HO-1 and VEGF were decreased,and the protein expression of Sesn2 was not significantlyaffected.The volume of cerebral infarction increased and neurological damage increased.(4)After interfering with Nrf2 and overexpressing Sesn2,the protein expression levels of angiogenesis-related proteins HO-1 and VEGF were decreased.Conclusion : Sesn2 may promote angiogenesis after cerebral ischemia by activating Nrf2/HO-1 pathway. |
PDF Full Text Request