Abstract: Objective To explore the protective effect of lutein on cranial nerve injury in rats exposed to manganese based on the nf-e2-related factor 2（Nrf2）-heme oxygenase-1（HO-1） pathway. Methods Totally 50 SD rats were divided into half and half of both sexes：control group,model group,low,medium and high dose lutein groups（40.0,80.0,160.0 mg/kg）. Except for the control group, all other groups of rats were given manganese sulfate solution（30 mg/kg） by gavage every day for 3 months. During the experiment, rats with low,medium and high doses of lutein were given corresponding doses of lutein by gavage every day,the control group and model group were given equal volumes of normal saline by gavage. After the experiment,the rats' neurological function indicators,neuronal apoptosis levels,superoxide dismutase（SOD）,glutathione（GSH）,lactate dehydrogenase（LDH）,reactive oxygen species（ROS）,and malondialdehyde（MDA） in hippocampal tissue were measured. Real-time fluorescence reverse transcription（RT-PCR） and Western blot were used to measure the levels of Nrf2,quinone oxidoreductase-1（NQO-1）,and HO-1 in hippocampal tissue. Results The pathway length,slope test score,hippocampal tissue SOD and GSH levels,and hippocampal tissue Nrf2,NQO-1, and HO-1 mRNA protein levels of rats in the manganese exposure group were lower than those in the control group,Longa nervous system score,modified neurological deficit score（mNSS） score,TdT-mediated dUTP nick end labeling（TUNEL） positive cells in the hippocampus,hippocampal tissue LDH,ROS,and MDA levels were higher than those in the control group,and the differences were statistically significant（all P<0.05）. After intervention treatment with low,medium,and high doses of lutein,the pathway length,slope test scores,SOD and GSH levels in hippocampal tissue,and Nrf2,NQO-1,and HO-1 mRNA protein levels in hippocampal tissue in each lutein dose group were higher than those in the manganese exposure group（0.86±0.07 vs 1.26±0.10, 1.56±0.17,2.84±0.23;0.53±0.06 vs 1.22±0.11,1.64±0.20,3.01±0.29;0.53±0.05 vs 1.18±0.14,1.82±0.19,3.14±0.30;0.28±0.03 vs 0.58±0.06,0.81±0.08,0.99±0.08;0.19±0.03 vs 0.31±0.04,0.63±0.07,1.03±0.09;0.21±0.02 vs 0.46±0.07,0.67±0.07,1.02±0.10,all P<0.05）,Longa nervous system score,mNSS score,number of TUNEL-positive cells in hippocampus,and hippocampal tissue LDH,ROS,and MDA levels were lower than those in the manganese exposure group,and the differences were statistically significant（all P<0.05）,and with the gradual increase of lutein dosage,the pathway length,slope test scores,SOD and GSH levels in hippocampal tissue,Nrf2,NQO-1,and HO-1 mRNA protein levels in hippocampal tissue gradually increased（1.26±0.10,1.56±0.17,2.84±0.23;1.22±0.11,1.64±0.20,3.01±0.29;1.18±0.14,1.82±0.19,3.14±0.30;0.58±0.06,0.81±0.08,0.99±0.08;0.31±0.04, 0.63±0.07,1.03±0.09;0.46±0.07,0.67±0.07,1.02±0.10）,Longa nervous system score,mNSS score,number of TUNEL-positive cells in hippocampus,LDH,ROS,and MDA levels in hippocampal tissue gradually decreased,and the dose-effect relationship was significant（all P<0.05）. Conclusion Lutein has a significant therapeutic effect on cranial nerve damage caused by manganese exposure,and its mechanism is related to the activation of the Nrf2-HO-1 pathway in the hippocampus of manganese exposed rats by lutein.

Key words: Nrf2, HO-1, Lutein, Manganese, Cranial nerve injury