Effects Of Selenium On Alleviating Cadmium-induced Autophagy In Rabbit Brain Based On Nrf2 Signaling Pathway

In order to reveal the effect of Se on Cd-induced autophagy in rabbit brain,forty3-month-old New Zealand white rabbits were randomly divided into 4 groups with 10 rabbits in each group.The following were control group,Cd(1 mg/kg BW),Se(0.5 mg/kg BW)and Cd(1 mg/kg BW)+Se(0.5 mg/kg BW)group,with a test period of 30 days.By observing the histopathological,ultrastructural,LC3 and Nrf2 immunofluorescence of the brain,determination of the main trace elements,antioxidant index,Nrf2 signaling pathway related gene and protein expression and autophagy related gene and protein expression in the brain tissue.The experiment result is given as:(1)Se can effectively inhibit brain damage by Cd.By observing the changes in histopathology and ultrastructure of brain tissue,it was found that Se improved the Cd-induced degenerative changes,including vacuolation,neuronal atrophy and other degenerative changes,and the structure and morphology of neurons were restored to normal,indicating that Se can reduce the brain damage caused by Cd.(2)Se antagonized Cd-induced the disturbance of trace elements.By the determination of Cd,Se,Cu,Zn,Fe and Ca in rabbit brain tissue,it was found that Se could significantly increase the contents of Cu and Fe compared to Cd group(P<0.05,P<0.01),and can significantly reduce the content of Cd(P<0.01).Compared with Cd group,Se can increase the content of Zn and Ca,but there is no significant difference.It is suggested that Se can antagonize the disturbance of trace elements caused by Cd.(3)Se antagonized oxidative damage induced by Cd.The expression of antioxidant enzymes and Nrf2 signaling pathway related genes and proteins in brain tissue was measured,the results showed that the activities of antioxidant enzymes(GSH-ST,GSH,T-SOD)in Cd+Se group were significantly increase compared with Cd group(P<0.01),the oxidation products(H₂O₂,MDA)were significantly decreased(P<0.05,P<0.01),the m RNA expression levels of Nrf2,HO-1 and NQO1 were significantly down-regulation(P<0.05),and the m RNA expression levels of Keap1 were significantly up-regulation(P<0.05).It suggested that Se may regulates the antioxidant defense system of brain tissue by activating the Nrf2 signaling pathway,and alleviates the oxidative stress caused by Cd.(4)Se antagonized Cd-induced autophagy.The m RNA levels of AMPK(Prkaa1,Prkaa2,Prkab1,Prkab1,Prkag2,Prkag3),Beclin1 and ATGs(ATG3,ATG5,ATG7,ATG12)and the protein levels of p AMPK/AMPK,LC3?/LC3?and Beclin1 in the brain tissue of rabbits treated with Cd and/or Se were determined.Meanwhile,LC3 immunofluorescence spots were observed.It was found that Se may alleviate Cd-induced autophagy in rabbit brain by affecting AMPK pathway.Conclusion:Se may regulates antioxidant enzymes by activating Nrf2 signaling pathway,and antagonizes Cd-induced oxidative stress and autophagy in brain by regulating AMPK signaling pathway.