慢性间歇性低氧对小鼠肝茶碱代谢的影响。

Effect of chronic intermittent hypoxia on theophylline metabolism in mouse liver.

机构信息

Department of Pulmonary Medicine, Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000, China.

出版信息

Chin Med J (Engl). 2013 Jan;126(1):118-23.

PMID:23286489

Abstract

BACKGROUND

Chronic intermittent hypoxia (CIH) has been associated with abnormalities in the liver, which is the most important organ for drug metabolism. This study aimed to investigate the effect of CIH on theophylline metabolism in mouse liver.

METHODS

Eight C57BL/6J mice were exposed to CIH for 12 weeks. Eight C57BL/6J mice were exposed to room air as a control group. Serum levels of alanine aminotransferase and aspartate aminotransferase were measured. Liver histology was observed by light and electron microscopy. Total hepatic cytochrome P450 concentration was measured. Hepatocytes were isolated and incubated with 15 mg/ml theophylline for four hours. After incubation, the theophylline concentration in the supernatant was measured and the theophylline metabolism rate was calculated.

RESULTS

CIH did not affect the serum transaminase levels. Livers from mice exposed to CIH showed hepatocellular edema, and liver cells had fuzzy rough endoplasmic reticulum under the electron microscope. The theophylline metabolism rate was significantly inhibited by CIH compared with controls; (16.60 ± 2.43)% vs. (21.58 ± 4.52)% (P = 0.02). The total liver cytochrome P450 concentration in the CIH group was significantly lower than in the control group; (0.83 ± 0.08) vs. (1.13 ± 0.21) mol/mg microsomal protein (P = 0.004).

CONCLUSION

CIH decreases theophylline metabolism by mouse hepatocytes, which may correlate with the downregulation of cytochrome P450 expression by CIH.

摘要

背景

慢性间歇性低氧（CIH）与肝脏异常有关，肝脏是药物代谢最重要的器官。本研究旨在探讨 CIH 对小鼠肝内茶碱代谢的影响。

方法

将 8 只 C57BL/6J 小鼠暴露于 CIH 中 12 周。8 只 C57BL/6J 小鼠暴露于室内空气中作为对照组。检测血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平。通过光镜和电镜观察肝组织学变化。测量总肝细胞色素 P450 浓度。分离肝细胞并与 15mg/ml 茶碱孵育 4 小时。孵育后，测量上清液中的茶碱浓度并计算茶碱代谢率。

结果

CIH 不影响血清转氨酶水平。暴露于 CIH 的小鼠肝脏显示肝细胞水肿，电镜下肝细胞内质网模糊。与对照组相比，CIH 显著抑制茶碱的代谢率；（16.60±2.43）%比（21.58±4.52）%（P=0.02）。CIH 组总肝细胞色素 P450 浓度明显低于对照组；（0.83±0.08）比（1.13±0.21）mol/mg 微粒体蛋白（P=0.004）。