The Activity And Expression Of CYP1A2,CYP2C11,CYP2C22 And CYP3A1 In Rats After Exposure To High Altitude Hypoxia

Objective: To investigate the the activity,protein and mRNA expression of CYP1A2,CYP2C11,CYP2C22 and CYP3A1 in rats after exposure to the natural hypoxia environment.Methods: Rats were divided by different heights,(1)control(P,390 m,20 kPa),(2)acute moderate altitude hypoxia(AMH,2 900 m,15.1 kPa),(3)chronic moderate altitude hypoxia(CMH,2 900 m,15.1 kPa),(4)acute high altitude hypoxia(AHH,4 300 m,12.4 kPa),(5)chronic high altitude hypoxia(CHH,4 300 m,12.4 kPa).Reversed-phase high performance liquid chromatography(RP-HPLC)was used to determine the concentration of caffeine,phenytoin,omeprazole,their metabolites,and 6-testosterone to evaluate the activity of CYP1A2,CYP2C11,CYP2C22,CYP3A1 in rats,respectively.We also evaluated the protein and mRNA expression of CYP450 s including CYP1A2,CYP2C11,CYP2C22,CYP3A1 by enzyme-linked immunosorbent assay and real-time quantitative PCR.Results: The activity of CYP1A2 in the acute moderate altitude hypoxia group,chronic moderate altitude hypoxia group,acute high altitude hypoxia group,chronic high altitude hypoxia group,were significantly decreased by 62.33%,60.75%,60.75% and 53.82%,respectively.The protein expression of CYP1A2 in the acute moderate altitude hypoxia group,chronic moderate altitude hypoxia group,acute high altitude hypoxia group,chronic high altitude hypoxia group,were significantly decreased by 56.26%、63.14%、59.08% and 62.08%,respectively.The mRNA expression of CYP1A2 in the acute moderate altitude hypoxia group,chronic moderate altitude hypoxia group,acute high altitude hypoxia group,chronic high altitude hypoxia group,were significantly decreased by 51.08%,37.23%,32.90% and 30.74%,respectively.The activities,protein expression and mRNA expression of CYP2C11 in the acute moderate altitude hypoxia group,chronic moderate altitude hypoxia group,acute high altitude hypoxia group,chronic high altitude hypoxia group,did not display significantly differences with those targets of P.The protein expressions and gene expressions of CYP2C22 in the acute moderate altitude hypoxia group,chronic moderate altitude hypoxia group,acute high altitude hypoxia group,chronic high altitude hypoxia group,were not significantly different with those of P,but the activity of CYP2C22 was significantly higher 117.65% under the special environment of acute high altitude hypoxia than those of the control.The activities and protein expression of CYP3A1 in the chronic moderate altitude hypoxia chronic high altitude hypoxia groups,were significantly lower than those of the plain,but there were no significant changes in the acute moderate altitude hypoxia and acute high altitude hypoxia groups.There was significantly less CYP3A1 activity by 43.02% and 50.00% in the chronic moderate altitude hypoxia chronic high altitude hypoxia groups,respectively,than those of the plain.The protein expression of CYP3A1 was 42.23% and 30.51% lower in the chronic moderate altitude hypoxia and chronic high altitude hypoxia groups,respectively,than in the P.The mRNA expression in the acute moderate altitude hypoxia group,chronic moderate altitude hypoxia group,chronic high altitude hypoxia group,were significantly decreased by 39.49%、32.63%、33.67%.Conclusion:(1)The activity,protein expression,and mRNA expression of CYP1A2 in AMH,CMH,AHH and CHH groups,were significantly decreased.(2)The activity,protein expression,mRNA expression of CYP2C11 in AMH,CMH,AHH and CHH groups,were not significantly different with those of P.(3)The protein expression,mRNA expression of CYP2C22 in AMH,CMH,AHH and CHH groups,were not significantly different with those of P,but the activity of CYP2C22 was significantly higher than those of P.(4)The activities and protein expression of CYP3A1 in CMH and CHH groups,were significantly lower than those of P,but there were no significant changes in AMH and AHH groups.The mRNA expression of CYP3A1 in AMH,CMH and CHH groups were significantly decreased,but it was not significantly different with those of P in AHH.