Type 2 diabetes is a high risk group for Alzheimers disease,so it is urgent to study the effective prevention target.Oxidative stress is one of the causes of Alzheimers disease.Heme oxygenase-1(HO-1)is one of the antioxidases in the brain.It can alleviate cellular oxidative damage by the removement of its metabolites(bilirubin)on active oxygen.Increased oxidative stress in brain induced by high blood free fatty acids in the diabetic state can also be alleviated by increasing the expression of HO-1,thus reducing the risk of type 2 diabetes complicated with Alzheimers disease.To make it clear,this study used free fatty acid to induce the BE(2)-M17 cells,one of neuroblastoma cells,to simulate the diabetic state,1)to investigate the pathway leading to the increased expression of HO-1;2)to observe the changes of cellular oxidative stress after the high expression of HO-1 was induced by an activator.DHE staining method and chemical luminescence method was used to detect cell active oxygen(reactive oxygen species(ROS)content in this study;real-time quantitative PCR was used to detect the mRNA expression of HO-1 and HO-1 upstream transcription factor Nrf2(erythroid-derived 2-like 2);western blot was used to detect the protein expression of HO-1,Nrf2 and Nrf2 upstream ERK and p-ERK protein levels;immunofluorescence staining was used to detect the nucleic localization of NRF2.Results showed that ROS was increased after palmitic acid treatment.Meanwhile,ERK was activated,the transfer of NRF2 into the nuclear was increased and the expression of HO-1 were up-regulated;ROS levels was reduced after HO-1 expression was further increased by a Nrf2 agonist,indicating that the up-regulation of HO-1 expression can reduce the neuronal oxidative stress induced by palmitic acid,which provides a new and important target for prevention of diabetic patients with Alzheimers disease.