慢性间歇性低氧小鼠模型中肝细胞色素P450 1A2（CYP1A2）表达降低。
Decreased expression of hepatic cytochrome P450 1A2 (CYP1A2) in a chronic intermittent hypoxia mouse model.
作者信息
Zhang Xiao-Bin, Zeng Yi-Ming, Chen Xiao-Yang, Zhang Yi-Xiang, Ding Jin-Zhen, Xue Cheng
机构信息
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Center of Respiratory Medicine of Fujian Province, Quanzhou 362000, China.
出版信息
J Thorac Dis. 2018 Feb;10(2):825-834. doi: 10.21037/jtd.2017.12.106.
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<0.01).
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.
背景
肝细胞色素P450（CYP）同工酶CYP1A2是多种药物代谢的重要酶之一。研究证实，持续性缺氧可影响肝脏CYP的表达，包括CYP1A2。慢性间歇性缺氧（CIH）作为睡眠呼吸暂停的一个显著特征，对CYP1A2的影响尚不清楚。本研究旨在评估CIH对睡眠呼吸暂停小鼠模型肝脏CYP1A2表达的影响。
方法
将24只6 - 8周龄的雄性C57BL/6J小鼠（每组n = 12）随机分为常氧组和CIH组。CIH组小鼠接受12周的间歇性缺氧暴露。通过定量实时聚合酶链反应分析两组肝脏CYP1A2的基因表达差异。采用蛋白质免疫印迹法和免疫组织化学法观察每组肝脏CYP1A2的蛋白水平。
结果
间歇性缺氧暴露12周后，CIH组肝脏CYP1A2在mRNA和蛋白水平的表达均比常氧组显著降低（P < 0.01）。
结论
CIH有助于抑制肝脏CYP1A2的表达。这意味着对于睡眠呼吸暂停患者，应由CYP1A2代谢的药物剂量应进行调整。
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