PPARγ provides anti-inflammatory and protective effects in intrahepatic cholestasis of pregnancy through NF-κB pathway

被引:22
作者
Zhang, Yan [1 ]
Huang, Xiaoping [1 ]
Zhou, Jie [1 ]
Yin, Yongxiang [1 ]
Zhang, Ting [1 ]
Chen, Daozhen [1 ]
机构
[1] Nanjing Med Univ, Wuxi Maternal & Child Hlth Hosp, Dept Gynecol & Obstet, Affiliated Hosp, Wuxi 214002, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Intrahepatic cholestasis of pregnancy; PPAR gamma; NF-kappa B; Oxidative stress; Inflammation; ACTIVATED RECEPTOR-GAMMA; ACIDS; INFLAMMATION;
D O I
10.1016/j.bbrc.2018.09.035
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Aims: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific hepatic disorder with potentially deleterious consequences of fetuses. Although the intimate relationship between ICP and peroxisome proliferator-activated receptor gamma (PPAR gamma) has been previously reported in physiological and pathological conditions, the detailed mechanisms in the process of intrahepatic cholestasis of pregnancy has been unclear. The aims of this study are to assess the role of PPAR gamma regulating the reactive oxygen species (ROS) and inflammation in the process of the ICP. Methods: Clinical data of the pregnant women were collected. And the serum of cytokines, hepatic function, the expression of PPAR gamma and NF-kappa B were measured. The rat and fetal rat ICP model were constructed and detection of the expression of PPAR gamma and NF-kappa B, evaluation the level of ROS and inflammation. Results: The clinical data showed that the new-born information in severe ICP group were significantly different as compared to that in control group (P < 0.05), and part of information in mild ICP group were also difference to that in control group (P < 0.05). The expression of PPAR gamma and NF-kappa B were significantly higher in clinical pregnant women, rat, fetal rat ICP model groups and taurocholate acid (TCA) treated HTR-8/SVneo cell (P < 0.01). PPAR gamma inhibited the production of ROS and decreased the level of inflammation. PPAR gamma down-regulated the NF-kappa B pathway. Conclusions: PPAR gamma provides the anti-inflammatory and protective effects in intrahepatic cholestasis of pregnancy through NF-kappa B pathway, which might be a probably one of the mechanisms of ICP. (C) 2018 Elsevier Inc. All rights reserved.
引用
收藏
页码:834 / 842
页数:9
相关论文
共 21 条
[1]   Bile Acids Induce Inflammatory Genes in Hepatocytes A Novel Mechanism of Inflammation during Obstructive Cholestasis [J].
Allen, Katryn ;
Jaeschke, Hartmut ;
Copple, Bryan L. .
AMERICAN JOURNAL OF PATHOLOGY, 2011, 178 (01) :175-186
[2]  
Aronica MA, 1999, J IMMUNOL, V163, P5116
[3]  
Arrese Marco, 2006, Ann Hepatol, V5, P202
[4]   Interleukin-6 Mediates the Increase in NADPH-Oxidase in the Ketamine Model of Schizophrenia [J].
Behrens, M. Margarita ;
Ali, Sameh S. ;
Dugan, Laura L. .
JOURNAL OF NEUROSCIENCE, 2008, 28 (51) :13957-13966
[5]   The influence of oxidative stress and autophagy cross regulation on pregnancy outcome [J].
de Andrade Ramos, Bruna Ribeiro ;
Witkin, Steven S. .
CELL STRESS & CHAPERONES, 2016, 21 (05) :755-762
[6]   Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation [J].
Du, QiaoLing ;
Pan, YouDong ;
Zhang, YouHua ;
Zhang, HaiLong ;
Zheng, YaJuan ;
Lu, Ling ;
Wang, JunLei ;
Duan, Tao ;
Chen, JianFeng .
BMC MEDICAL GENOMICS, 2014, 7
[7]   Intrahepatic Cholestasis of Pregnancy A Critical Clinical Review [J].
Gabzdyl, Elizabeth M. ;
Schlaeger, Judith M. .
JOURNAL OF PERINATAL & NEONATAL NURSING, 2015, 29 (01) :41-50
[8]   Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications - a review [J].
Grygiel-Gorniak, Bogna .
NUTRITION JOURNAL, 2014, 13
[9]  
Hatami Mehdi, 2016, Chonnam Med J, V52, P201, DOI 10.4068/cmj.2016.52.3.201
[10]   Intrahepatic cholestasis of pregnancy (ICP): case report and review of the literature [J].
Keitel, V. ;
Droege, C. ;
Stepanow, S. ;
Fehm, T. ;
Mayatepek, E. ;
Koehrer, K. ;
Haeussinger, D. .
ZEITSCHRIFT FUR GASTROENTEROLOGIE, 2016, 54 (12) :1327-1333