Study Of Expression Of NF-E2-related Factor 2-antioxidant Response Elements Pathway In The Artery After Subarachnoid Hemorrhage And The Correlation With Cerebral Vasospasm

Background and objective:The pathogenesis of cerebral vasospasm(CVS) after subarachnoid hemorrhage(SAH) is complicated.lt is suggested to include endothelial damage,oxidative stress,inflammatory damage and accumulation of toxic metabolites by rescent studies.NF-E2-related factor 2(Nrf2) plays a important role during many pathological stress processes.lt is eventful for prevention and therapy of CVS to study expression of Nrf2-antioxidant response elements(ARE) pathway in the artery after SAH and the relationship with CVS.Methods:48 rabbits were randomly assigned to four groups.Every group was randomly assigned to two groups:6 rabbits each group for histological or molecular biological examination respectively. The methods of two-time blood injection into occipital cistern"were used to construct rabbit SAH models.The animals of SAH day 3,day 5,day 7 groups were killed on days 3,5,and 7,respectively.The basilar arteries of entire length were reserved.Immunohistochemistry and Western blot analysis were used to assess the Nrf2 expression.The mRNA levels of Nrf2 were determined by RT-PCR.The activities of Glutathione peroxidase(Gpx) in the arteries were measured.Cross-sectional area of basilar artery was measured to assess the level of CVS.Result:The basilar arteries exhibited vasospasm after SAH and became more severe on days 3 and 5. The elevated expression of Nrf2 was detected after SAH and peaked on days 3 and 5 via immunohistochemistry and Western blot analysis(P<0.05,respcetively). Immunoreactivity of Nrf2 was mainly present in the endothelial cells and the smooth muscle. Nrf2 mRNA was increasingly expressed after SAH,not in a parallel time course to the development of CVS.The activities of Gpx decreased(P<0.05),minimum on days 3 and 5.The correlation of immunoreactivity score and Western blot analysis of Nrf2 with cross-sectional area of basilar artery are positive respcetively (r=-0.898 and-0.791,P<0.05, respcetively). The correlation of activities of Gpx with cross-sectional area of basilar artery are negtive (r=0.906,P<0.05)Conclusion: The study demostrateed the elevated expression of Nrf2 in the wall of basilar artery of rabbit SAH model.It maybe suggests a important role of Nrf2 in the pathophysiologic mechanism of CVS after SAH.However,CVS did not release in pace with the up-regulation expression of Nrf2.Meanwhile,the activities of Gpx,which is the very important product of Nrf2-ARE pathway,decreased in a parallel time course to the development of CVS.Therefore,the role of Nrf2-ARE pathway in CVS calls for further study.