Decreased expression of hepatic cytochrome P450 1A2 (CYP1A2) in a chronic intermittent hypoxia mouse model

摘要

Background: Hepatic cytochrome P450 (CYP) isoforms, CYP1A2, is one of important enzymes for many drugs metabolism. Studies have confirmed that sustained hypoxia can influence the expression of hepatic CYP, including CYP1A2. The impact of chronic intermittent hypoxia (CIH), a marked characteristic of sleep apnea, on CYP1A2 remains unclear. The aim of the present study was to evaluate the effect of CIH on the expression of hepatic CYP1A2 in a mouse model with sleep apnea. Methods: Twenty four old male (6–8 weeks) C57BL/6J mice (n=12 in each group) were randomly assigned to either normoxia group or CIH group. Mice in CIH group underwent 12 weeks intermittent hypoxia exposure. The different gene expression of hepatic CYP1A2 between two groups was analyzed by quantity real-time polymerase chain reaction. The protein levels of hepatic CYP1A2 in each group were observed by using western blotting and immunohistochemistry. Results: After 12 weeks of exposure to intermittent hypoxia, the expression of hepatic CYP1A2, at the mRNA and protein levels was decreased more significantly in the CIH group than the normoxia group (P Conclusions: CIH contributes to inhibiting the expression of hepatic CYP1A2. This implies that the dosage of drugs metabolized by CYP1A2, should be adjusted in patients with sleep apnea.