Effect of recombinant adenovirus hypoxia-inducible factor 1α on glucose metabolism and neurological function in the CA1 region of hippocampus with cerebral ischemia
Objective To investigate the impact of exogenous hypoxia-inducible factor 1α(HIF-1α)on glucose metabolism-related proteins and neurological function in the hippocampal CA1 region of rats with cerebral ischemia.Methods Adult male SD rats were randomly assigned to four groups:sham operation group(Sham group),cerebral ischemia reperfusion group(CIR group),recombinant adenovirus empty vector intervention group(Ad group),and recombinant adenovirus HIF-1α gene intervention group(AdHIF-1α group),each consisting of 12 rats.A rat model of cerebral ischemia-reperfusion injury was induced using the modified suture method,and neurological deficits were assessed using the Longa method.In line with previous protocols,exogenous Ad and AdHIF-1α were introduced into the lateral ventricle of rats in the Ad and AdHIF-1α groups,respectively.After 28 days of observation,the animals were euthanized.Hippocampal tissue was collected for analysis,including Hematoxylin-eosin(HE)staining,terminal transferase labeling in situ(TUNEL)staining,and Nissl staining to evaluate pathological changes and neuronal survival in the hippocampal CA1 region.Western blot was performed to assess the expression levels of HIF-1α,glucose transporter 1(GLUT1),glucose transporter 3(GLUT3),and 6-phosphofructose-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3)proteins in the hippocampal tissue.Results Following 28 days of recombinant adenovirus HIF-1α gene therapy,rats in the AdHIF-1α group exhibited reduced neurological deficits compared to the CIR group(P＜0.05).Histopathological analysis of nerve cells in the CA1 region of the hippocampus showed significant improvement,with an increase in the number of surviving nerve cells and a decrease in apoptotic cells(P＜0.01).Western blot results indicated an upregulation of HIF-1α expression in the hippocampus of the CIR group compared to the Sham group,along with increased levels of glucose metabolism-related proteins(GLUT1,GLUT3,and PFKFB3)(all P＜0.05).Furthermore,elevating HIF-1α expression through AdHIF-1α led to a further increase in the expression of glucose transporters(GLUT1,GLUT3,and PFKFB3)in the AdHIF-1α group,demonstrating statistically significant differences compared to the CIR group(all P＜0.05).Notably,there were no statistically significant variances in the aforementioned parameters between the Ad group and the CIR group(all P＞0.05).Conclusions The AdHIF-1α gene has the potential to enhance neurological function,promote nerve cell survival,and decrease nerve cell apoptosis.This effect is likely achieved by increasing HIF-1α expression in the hippocampus,subsequently up-regulating GLUT1,GLUT3 and PFKFB3 expression,and ultimately improving glucose metabolism supply.Overall,this gene shows promise in protecting the brain.
NETL
NSTL
万方数据
