Chiba Tsuyoshi, Noji Keiko, Shinozaki Shohei, Suzuki Sachina, Umegaki Keizo, Shimokado Kentaro
Information Center, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan.
Department of Vascular Medicine and Geriatrics, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
J Pharm Pharmacol. 2016 Dec;68(12):1567-1576. doi: 10.1111/jphp.12646. Epub 2016 Oct 19.
Non-alcoholic fatty liver disease (NAFLD) is associated with impaired liver function, and resveratrol could suppress NAFLD progression. This study examined the effects of NAFLD on the expression of major cytochrome P450 (CYP) subtypes in the liver and whether the expression could be attenuated by resveratrol.
C57BL/6 mice (male, 10 weeks of age) were fed a high-fat and high-sucrose (HFHS) diet to induce NAFLD. Major Cyp subtype mRNA expression in the liver was measured by real-time RT-PCR.
Body and liver weights at 4 and 12 weeks were significantly higher in mice fed the HFHS diet compared with control. The HFHS diet significantly increased the accumulation of cholesterol and triglycerides at 12 weeks. Under this condition, the HFHS diet increased the expression of Cyp1a2 and decreased that of Cyp3a11 at 1 week and thereafter. On the other hand, Cyp1a1, 2b10 and 2c29 mRNA expression levels in the liver were significantly increased at 12 weeks only. Resveratrol (0.05% (w/w) in diet) slightly suppressed lipid accumulation in the liver, but failed to recover impaired Cyp gene expression levels in NAFLD.
Drug metabolism may be impaired in NAFLD, and each Cyp subtype is regulated in a different manner.
非酒精性脂肪性肝病（NAFLD）与肝功能受损相关，白藜芦醇可抑制NAFLD的进展。本研究检测了NAFLD对肝脏中主要细胞色素P450（CYP）亚型表达的影响，以及白藜芦醇是否能减弱这种表达。
给10周龄雄性C57BL/6小鼠喂食高脂高糖（HFHS）饮食以诱导NAFLD。通过实时逆转录聚合酶链反应（RT-PCR）检测肝脏中主要Cyp亚型mRNA的表达。
与对照组相比，喂食HFHS饮食的小鼠在4周和12周时的体重和肝脏重量显著更高。HFHS饮食在12周时显著增加了胆固醇和甘油三酯的积累。在这种情况下，HFHS饮食在1周及之后增加了Cyp1a2的表达并降低了Cyp3a11的表达。另一方面，肝脏中Cyp1a1、2b10和2c29的mRNA表达水平仅在12周时显著增加。白藜芦醇（饮食中0.05%（w/w））略微抑制了肝脏中的脂质积累，但未能恢复NAFLD中受损的Cyp基因表达水平。
NAFLD中药物代谢可能受损，且每种Cyp亚型的调节方式不同。
