孕期野百合碱暴露对胎鼠胆固醇水平的影响

中国药物警戒 ›› 2019, Vol. 16 ›› Issue (2): 71-75.

• 吡咯里西啶生物碱的发育毒性专栏 • 上一篇下一篇

孕期野百合碱暴露对胎鼠胆固醇水平的影响

郭麒^1,2, 王艳清³, 程艳香³, 刘杰^1,2, 邱帅凯^1,2, 向娥^1,2, 汪晖^1,2, 郭喻^1,2,*

1 武汉大学基础医学院药理学系,湖北武汉 430071;
2 发育源性疾病湖北省重点实验室,湖北武汉 430071;
3 武汉大学人民医院妇产科,湖北武汉 430060

收稿日期:2019-03-12 修回日期:2019-03-12 出版日期:2019-02-25 发布日期:2019-03-12
作者简介:郭麒,女,在读硕士,药理学。

ffects of Exposure to Monocrotaline on Cholesterol Levels of Fetal Rats

GUO Qi^1,2, WANG Yanqing³, CHENG Yanxiang³, LIU Jie^1,2, QIU Shuaikai^1,2, XIANG E^1,2, WANG Hui^1,2, GUO Yu^1,2,*

1 Department of Pharmacology, Basic Medical School of Wuhan University, Hubei Wuhan 430071, China;
2 Hubei Provincial Key Laboratory of Developmentally Originated Disease, Hubei Wuhan 430071, China;
3 Department of Gynecology, Renming Hospital of Wuhan University, Hubei Wuhan 430060, China

Received:2019-03-12 Revised:2019-03-12 Online:2019-02-25 Published:2019-03-12
Contact: *郭喻,女,副教授,发育毒理学。E-mail：guoy@whu.edu.cn
Supported by:
国家自然科学基金（81473290）：吡咯里西啶生物碱致母、胎肝毒性差异及其代谢活化机制; 国家自然科学基金青年项目（30901835）：胎肾上腺CYP3A介导吡咯双环生物碱类发育毒性的代谢损伤机制; 中央高校基本科研业务费专项（2042017Kf1032）：吡咯里西啶生物碱致发育毒性的性别差异及其机制研究

摘要/Abstract

摘要： 目的研究孕期野百合碱（monocrotaline,MCT）暴露的胎鼠胆固醇水平改变及其原因。方法受孕Wistar大鼠于孕9~20天（gestation day,GD）每天灌胃给予20 mg·kg-1 MCT,孕鼠于GD 20处死,取雌雄性胎鼠并收集母胎血、胎盘和胎肝,检测母血胆汁酸及母、胎血胆固醇水平,以及胎盘胆固醇转运和胎肝胆固醇合成、转运相关基因表达。结果与对照组相比,MCT组母血胆汁酸水平增高,总胆固醇（total cholesterol,TCH）水平升高。雄性胎血TCH和低密度脂蛋白胆固醇（low density lipoprotein cholesterol,LDL-C）水平升高,雌雄性胎盘低密度脂蛋白受体（low-density lipoprotein receptor,LDLR）、B类I型清道夫受体（scavenger receptor class B type I,SR-B1）、三磷酸腺苷结合盒转运体A1（adenosine triphosphate binding cassette transporter A1,ABCA1）基因表达上调,而雌雄性胎肝3-羟基-3-甲基戊二酰辅酶A还原酶（3-hydroxy-3-methylglutaryl coenzyme A reductase,HMGCR）、SR-B1、LDLR mRNA表达下调。结论孕期MCT暴露所致母鼠血胆汁酸水平增高可引起母鼠高胆固醇血症,增加胎盘胆固醇转运体表达,导致胎鼠高胆固醇血症。胎肝胆固醇转运相关基因表达降低,提示孕期MCT暴露可造成胎肝的胆固醇代谢稳态改变。

关键词: 孕期, 野百合碱, 妊娠期胆汁淤积, 胆固醇转运

Abstract: Objective To explore the changes and causes of cholesterol level in fetal rats from cholestasis mother induced by monocrotaline (MCT) exposure. Methods Pregnant Wistar rats were treated with MCT(20 mg·kg-1·d-1) from gestation days (GDs) 11 to 20, and rats were sacrificed at GD 20. Maternal and fetal blood, placenta and fetal liver were collected. Cholesterol levels in maternal and fetal bloods were determined, and expression of placental cholesterol transporter and fetal liver cholesterol-related genes were examined. Results Compared with the control group, maternal blood bile acid and total cholesterol (TCH) levels were enhanced by MCT treatment. Male fetal blood TCH and low-density lipoprotein cholesterol (LDL-C) levels increased. Expression of low-density lipoprotein receptor (LDLR), scavenger receptor class B type I (SR-B1) and triphosphate binding cassette transporter A1 (ABCA1) were up-regulated in male and female fetal placentae from MCT group. In addition, expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), SR-B1, and LDLR were down-regulated in male and female fetal liver. Conclusion Maternal cholestasis induced by MCT exposure caused hypercholesterolemia in maternal and increased the expression of placental cholesterol transporter, leading to a high cholesterol level in fetal rats. Changes in the expression of cholesterol transporter in fetal liver suggest that MCT exposure during pregnancy may result in alteration of cholesterol homeostasis in fetal liver.

Key words: pregnancy, monocrotaline, intrahepatic cholestasis of pregnancy, cholesterol transport

中图分类号:

R961

郭麒, 王艳清, 程艳香, 刘杰, 邱帅凯, 向娥, 汪晖, 郭喻. 孕期野百合碱暴露对胎鼠胆固醇水平的影响[J]. 中国药物警戒, 2019, 16(2): 71-75.

GUO Qi, WANG Yanqing, CHENG Yanxiang, LIU Jie, QIU Shuaikai, XIANG E, WANG Hui, GUO Yu. ffects of Exposure to Monocrotaline on Cholesterol Levels of Fetal Rats[J]. Chinese Journal of Pharmacovigilance, 2019, 16(2): 71-75.

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孕期野百合碱暴露对胎鼠胆固醇水平的影响

ffects of Exposure to Monocrotaline on Cholesterol Levels of Fetal Rats

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