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Hepatic Cyp1a2 Expression Reduction during Inflammation Elicited in a Rat Model of Intermittent Hypoxia

摘要Background: Intermittent hypoxia (IH) is a key element of obstructive sleep apnea (OSA) that can lead to disorders in the liver. In this study, IH was established in a rat model to examine its effects on the expression of hepatic cytochrome P450 (CYP) and CYP regulators, including nuclear receptors. Methods: Hematoxylin and eosin staining was conducted to analyze the general pathology of the liver of rats exposed to IH. The messenger RNA (mRNA) expression levels of inflammatory cytokines, CYPs, nuclear factor?κB (NF?κB), and nuclear factors in the liver were measured by quantitative reverse transcription polymerase chain reaction. Results: We found inflammatory infiltrates in the liver of rats exposed to IH. The mRNA expression level of interleukin?1beta was increased in the liver of the IH?exposed rats (0.005 ± 0.001 vs. 0.038 ± 0.008, P = 0.042), whereas the mRNA expression level of Cyp1a2 was downregulated (0.022 ± 0.002 vs. 0.0050 ± 0.0002, P = 0.029). The hepatic level of transcription factor NF?κB was also reduced in the IH group relative to that in the control group, but the difference was not statistically significant and was parallel to the expression of the pregnane X receptor and constitutive androstane receptor. However, the decreased expression of the glucocorticoid receptor upon IH treatment was statistically significant (0.056 ± 0.012 vs. 0.032 ± 0.005, P = 0.035). Conclusions: These results indicate a decrease in expression of hepatic CYPs and their regulator GR in rats exposed to IH. Therefore, this should be noted for patients on medication, especially those on drugs metabolized via the hepatic system, and close attention should be paid to the liver function of patients with OSA?associated IH.

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作者单位 Department of Respiratory Medicine, Haihe Clinical College of Tianjin Medical University, Tianjin 300350, China [1] Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Haihe Hospital, Tianjin 300350, China [2] Department of Basic Medicine, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin 300350, China [3]
栏目名称 Original Articles
DOI 10.4103/0366?6999.217084
发布时间 2017-12-06
基金项目
grants from the National Natural Science Foundation of China the Natural Science Foundation of Tianjin Key Projects of Health and Family Planning Commission of Tianjin
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中华医学杂志(英文版)

中华医学杂志(英文版)

2017年21期

2585-2590页

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