首页|PXR、PPARα激动所致小鼠肝增大的昼夜节律研究

PXR、PPARα激动所致小鼠肝增大的昼夜节律研究

扫码查看
肝脏大小受生物钟控制并具有昼夜节律。孕烷X受体(pregnane X receptor,PXR)和过氧化物酶体增殖物激活受体α(peroxisome proliferator-activated receptor α,PPARα)是核受体超家族的重要成员。本课题组前期发现,鼠源激动剂孕烯醇酮 16α-腈(pregnenolone 16α-carbonitrile,PCN)激动 PXR、匹立尼酸(pirinixic acid,WY-14643)激动PPARα后均显著促进小鼠生理性肝增大及部分肝切除术后肝再生。但是,PXR、PPARα激动所致肝增大的昼夜变化尚不清楚。因此,本研究考察连续3天不同时辰给予雄性C57BL/6小鼠玉米油、PCN或WY-14643后肝脏大小及生物钟相关基因等的变化。本动物实验方案经中山大学实验动物伦理委员会审核批准(批准号:SYSU-IACUC-2023-001613、SYSU-IACUC-2023-001783)。结果表明,连续3天不同时辰给予PXR、PPARα激动剂均显著促进小鼠肝增大,其所致肝增大与肝脏大小本身的昼夜节律基本一致,且基本不影响生物钟相关基因的表达,提示PXR、PPARα激动可能不影响肝脏大小本身的昼夜节律。本研究阐明了 PXR、PPARα激动所致肝增大的昼夜节律,为核受体促进肝增大及肝脏大小昼夜节律的研究提供新数据和参考。
Diurnal rhythm of PXR or PPARα activation-induced liver enlargement
Liver size is regulated by circadian clock and exhibits a diurnal rhythm.Pregnane X receptor(PXR)and peroxisome proliferator-activated receptor α(PPARα),members of nuclear receptor superfamily,are important regulators of liver size.We previously demonstrated that mPXR agonist pregnenolone 16α-carbonitrile(PCN)and mPPARα agonist pirinixic acid(WY-14643)promoted liver enlargement and liver regeneration after partial hepatectomy.However,whether PXR or PPARα activation-induced liver enlargement exhibits diurnal rhythm with normal liver diurnal oscillations remains unclear.The aim of this study was to investigate the diurnal rhythm of PXR or PPARα activation-induced liver enlargement.Male C57BL/6 mice were intraperitoneally injected with corn oil,PCN or WY-14643 for three days,and liver samples were weighed and collected at various time points for analysis.The animal experiment protocol was reviewed and approved by Institutional Animal Care and Use Committee of Sun Yat-sen University(approval No.SYSU-IACUC-2023-001613,SYSU-IACUC-2023-001783).The results showed that PXR or PPARα activation at various time points significantly induced liver enlargement,and liver size maintained normal diurnal oscillations during PXR or PPARα activation-induced hepatomegaly,without significant effects on the expression of core clock genes.This study reveals PXR or PPARα activation-induced liver enlargement exhibits diurnal rhythm with normal liver diurnal oscillations,and provides novel data for nuclear receptor-induced liver enlargement and liver diurnal rhythm.

pregnane X receptorperoxisome proliferator-activated receptor αnuclear receptorliver enlargementdiurnal rhythm

冼图、田佳宁、李宣、范仕成、蔡承晖、赵鹏飞、黄民、毕惠嫦

展开 >

中山大学药学院,广东 广州 510006

南方医科大学药学院,广东 广州 510515

孕烷X受体 过氧化物酶体增殖物激活受体α 核受体 肝增大 昼夜节律

2024

药学学报
中国药学会 中国医学科学院药物研究所

药学学报

CSTPCD北大核心
影响因子:1.274
ISSN:0513-4870
年,卷(期):2024.59(12)