The Effect Of Interminent Hypoxic Exposure For 4 Weeks On Antioxidant Enzymes Expression In Skeletal Muscle Of Nrf2 Knock-out Mice

Objective:Intermittent hypoxic has an antioxidant protective effect and can improve the cardiovascular system of chronic disease to a certain extent.Nrf2 is a key nuclear transcription factor that regulates the anti-oxidative response and plays a crucial role in the body's defense against oxidative stress.It is not clear whether Nrf2 plays a key role and mediates a series of changes in the expression of antioxidant enzymes during the process of intermittent hypoxic exposure to skeletal muscle.In this study,wild type mice and Nrf2 knockout mice were exposed to hypoxic,to explore the effect of four weeks' intermittent hypoxic exposure mediated Nrf2 on expressions of antioxidant enzyme.Methods: Twenty healthy wild C57BL/6J mouse(WT)and twenty Nrf2 knock-out mouse(Nrf2 KO)were randomly divided into two groups: normoxic(NW,NK)and hypoxic(HW,HK)exposure groups.There were 4 groups totally which each group had 10 mouse with half male and half female.The normoxic groups were kept in normoxic environment for four weeks.Hypoxic groups were exposed to hypoxic in animal hypoxic room at low oxygen concentration of 10.2%(simulated altitude of about 5000 meters),and the exposure time ranged from 8:00-16:00 every day for 8 hours for four weeks.Hypoxic groups were sacrificed for sampling at the end of 48 hours after the last hypoxic exposure with the normoxic groups.Western blot was used to determine the expression of skeletal muscle antioxidant enzymes,which contain HIF-1?,CAT,SOD1,SOD2,HO-1,NQO-1,GCLc,GPx-1 and GR.The content of ROS in skeletal muscle was determined with the kit.Results:(1)Compared with group HW,the relative expression of SOD1 and SOD2 in HW groups were significantly decreased(P<.01)and HO-1 was significantly increased(P<.01).(2)Compared with NK,the relative expression of CAT,SOD1,SOD2 and GClc in HK group was significantly decreased(P<.01),while the expression of HO-1 was significantly increased(P<.01).(3)HK compared with HW,the expressions of SOD1,and NQO-1 showed a significant decrease(P<.05),GCLc showed a very significant decrease(P<.01).Conclusion:(1)The change of the expression of antioxidant enzymes in skeletal muscles of wild mice which affected by the intermittent oxygen exposure for 4 weeks at 10.2% oxygen concentration was irregular.(2)The loss of Nrf2 had no effect on the expression of antioxidant enzymes in skeletal muscle under normoxia,but the loss of Nrf2 could further reduce the expression of some antioxidant enzymes under hypoxia.