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中华妇幼临床医学杂志(电子版) ›› 2015, Vol. 11 ›› Issue (01) : 9 -13. doi: 10.3877/cma.j.issn.1673-5250.2015.01.003

所属专题: 文献

论著

母体肥胖对人胎盘P-糖蛋白表达水平的影响
詹雅兰1, 王川1, 周开宇2, 刘兴会3, 李一飞1, 华益民4,*,*(), 母得志2   
  1. 1. 610041 成都,四川大学华西第二医院儿科;610041 成都,四川大学华西临床医学院
    2. 610041 成都,四川大学华西第二医院儿科
    3. 610041 成都,四川大学华西第二医院产科
    4. 610041 成都,四川大学华西第二医院儿科;610041 成都,四川大学华西第二医院肺血管重构实验室
  • 收稿日期:2014-11-14 修回日期:2014-12-18 出版日期:2015-02-01
  • 通信作者: 华益民

Effect of maternal obesity on the expression level of P-glycoprotein in human placenta

Yalan Zhan1, Chuan Wang1, Kaiyu Zhou2, Xinghui Liu3, Yifei Li1, Yiming Hua4(), Dezhi Mu2   

  1. 1. Department of Pediatrics Vascular Remodeling Research Unit, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China; West China Medical School of Sichuan University, Chengdu 610041, Sichuan Province, China
    2. Department of Pediatrics Vascular Remodeling Research Unit, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
    3. Department of Obstetrics Vascular Remodeling Research Unit, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
    4. Department of Pediatrics Vascular Remodeling Research Unit, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China; Department of Pulmonary Vascular Remodeling Research Unit, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2014-11-14 Revised:2014-12-18 Published:2015-02-01
  • Corresponding author: Yiming Hua
  • About author:
    Corresponding author: Hua Yimin, Email:
引用本文:

詹雅兰, 王川, 周开宇, 刘兴会, 李一飞, 华益民, 母得志. 母体肥胖对人胎盘P-糖蛋白表达水平的影响[J]. 中华妇幼临床医学杂志(电子版), 2015, 11(01): 9-13.

Yalan Zhan, Chuan Wang, Kaiyu Zhou, Xinghui Liu, Yifei Li, Yiming Hua, Dezhi Mu. Effect of maternal obesity on the expression level of P-glycoprotein in human placenta[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2015, 11(01): 9-13.

目的

评估母体肥胖对人体胎盘中P-糖蛋表达水平的影响,为制定地高辛产前干预胎儿心力衰竭个体化给药方案提供理论依据。

方法

选择2013年3~6月,在四川大学华西第二医院产科分娩的25例孕期正常且足月妊娠的产妇为研究对象,按照孕前体质指数(BMI)将其分为:肥胖组(n=10,BMI≥27.9 kg/m2)及正常组(n=15,18.5 kg/m2≤BMI<23.9 kg/m2)。在孕妇分娩时获取其自然娩出的胎盘组织,对其采用实时荧光定量聚合酶链反应(RT-PCR)与Western blotting法检测P-糖蛋白的编码基因ABCB1的ABCB1 mRNA及P-糖蛋白相对表达量,并进行统计学分析。本研究遵循的程序符合四川大学华西第二医院人体试验委员会制定的伦理学标准,得到该委员会批准,分组征得受试对象知情同意,并与之签署临床研究知情同意书。

结果

①肥胖组孕前及产时BMI均显著高于正常组,且差异有统计学意义(t=20.88,11.66;P<0.001);而两组间母亲年龄、孕龄、孕次及产次,新生儿性别构成比、出生体质量及身长,胎盘重量比较,差异均无统计学意义(P>0.05)。②肥胖组胎盘组织中ABCB1 mRNA及P-糖蛋白相对表达量均显著低于正常组,且差异有统计学意义(t=-2.146, P=0.043;t=-3.862,P=0.005)。

结论

母体肥胖可能使孕期用药时胎儿侧血药浓度升高,在制定地高辛产前干预胎儿心力衰竭个体化给药方案时,应减少母体肥胖者地高辛用药剂量。

Objective

To evaluate the effect of maternal obesity on the expression level of P-glycoprotein in human placenta, and to provide a theoretical basis for individualized dosage regimen of digoxin prenatal intervention for fetal heart failure.

Methods

A total of 25 puerperants with normal and full-term pregnancy in West China Second University Hospital, Sichuan University from March to June 2013 were chosen as study subjects.In accordance with the pre-pregnancy body mass index(BMI), they were divided into obesity group(n=10, BMI≥27.9 kg/m2)and control group(n=15, 18.5 kg/m2≤BMI<23.9 kg/m2). Placentas were collected at birth.The relative expression levels of ABCB1 mRNA and P-glycoprotein in the placenta were determined by the methods of real-time polymerase chain reaction (RT-PCR) and Western blotting, and the data were analyzed statistically.The study protocol was approved by the Ethical Review Board of Investigation in Human Being of West China Second University Hospital, Sichuan University.Informed consent was obtained from each participant.

Results

①Both the pre-pregnancy BMI and BMI at birth of obesity group were significantly higher than those of control group(t=20.88, 11.66; P<0.001); but there were no significant differences between two groups in maternal age, gestational age, gravidity, parity, constituent ratio of neonatal sex, neonatal weight, neonatal body length and placental weight(P>0.05). ②The relative expression levels of ABCB1 mRNA and P-glycoprotein in placenta of obesity group were both significantly lower than those of control group(t=-2.146, P=0.043; t=-3.862, P=0.005).

Conclusions

The digoxin concentration in fetal compartment might increase in obese mothers during pregnancy, suggesting that lower dosage of digoxin should be given to obese pregnant women when given prenatal intervention for fetal heart failure.

表1 两组产妇及其新生儿一般临床资料比较(±s)
Table 1 Comparison of maternal and neonatal general clinical data between two groups(±s)
图1 两组胎盘组织中ABCB1 mRNA相对表达量比较
Figure 1 Comparison of relative expressions of placental ABCB1 mRNA between two groups
图2 两组胎盘组织中P-糖蛋白Western blotting结果
Figure 2 Western blotting results of placental P-glycoprotein of two groups
图3 两组胎盘组织中P-糖蛋白相对表达量比较
Figure 3 Comparison of relative expressions of placental P-glycoprotein between two groups
表2 两组产妇胎盘组织中ABCB1 mRNA及P-糖蛋白相对表达量比较(±s)
Table 2 Comparison of relative expression levels of ABCB1 mRNA and P-glycoprotein in placentas between two groups(±s)
[1]
Andrade SE,Gurwitz JH,Davis RL,et al. Prescription drug use in pregnancy[J]. Am J Obstet Gynecol,2004,191(2):398–407.
[2]
Ceckova-Novotna M,Pavek P,Staud F. P-glycoprotein in the placenta: expression, localization,regulation and function[J].Reprod Toxicol,2006,22(3):400–410.
[3]
Holcberg G,Sapir O,Tsadkin M,et al.Lack of interaction of digoxin and P-glycoprotein inhibitors,quinidine and verapamil in human placenta in vitro[J]. Eur J Obstet Gynecol Reprod Biol,2003,109(2):133–137.
[4]
Wang C,Li H,Zhou K,et al. Sodium tanshinone ⅡA sulfonate and sodium danshensu open the placental barrier through down-regulation of placental P-glycoprotein in mice: implications in the transplacental digoxin treatment for fetal heart failure[J].Int J Cardiol,2014,176(3):1331–1333.
[5]
Anger GJ,Cressman AM,Piquette-Miller M. Expression of ABC Efflux transporters in placenta from women with insulin-managed diabetes[J].PLoS One,2012,7(4):e35027.
[6]
Soo PS,Hiscock J,Botting KJ,et al.Maternal undernutrition reduces P-glycoprotein in guinea pig placenta and developing brain in late gestation[J].Reprod Toxicol,2012,33(3):374–381.
[7]
Lumeng CN,Bodzin JL,Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization[J].J Clin Invest,2007,117(1):175–184.
[8]
Challier JC,Basu S,Bintein T, et al. Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta[J]. Placenta,2008,29(3):274–281.
[9]
Ramsay JE,Ferrell WR,Crawford L,et al. Maternal obesity is associated with dysregulation of metabolic,vascular,and inflammatory pathways[J].J Clin Endocrinol Metab,2002,87(9):4231–4237.
[10]
Evseenko DA,Paxton JW,Keelan JA.Independent regulation of apical and basolateral drug transporter expression and function in placental trophoblasts by cytokines, steroids, and growth factors[J].Drug Metab Dispos,2007,35(4):595–601.
[11]
Petrovic V,Piquette-Miller M.Impact of polyinosinic/polycytidylic acid on placental and hepatobiliary drug transporters in pregnant rats[J]. Drug Metab Dispos,2010,38(10):1760–1766.
[12]
Zatelli MC,Molè D,Tagliati F,et al. Cyclo-oxygenase 2 modulates chemoresistance in breast cancer cells involving NF-kappaB[J]. Cell Oncol,2009,31(6):457–465.
[13]
Cygalova L,Ceckova M,Pavek P,et al. Role of breast cancer resistance protein (Bcrp/Abcg2) in fetal protection during gestation in rat[J]. Toxicol Lett, 2008, 178(3):176–180.
[14]
Scotto KW.Transcriptional regulation of ABC drug transporters[J]. Oncogene, 2003,22(47):7496–7511.
[15]
Sukhai M,Yong A,Pak A,et al.Decreased expression of P-glycoprotein in interleukin-1beta and interleukin-6 treated rat hepatocytes[J].Inflamm Res,2001,50(7):362–370.
[16]
张洁,王方,许海燕,等.炎性因子与胰岛素抵抗[J].世界华人消化杂志,2006,14(32): 3121–3125.
[17]
Liu H,Yang H,Wang D,et al.Insulin regulates P-glycoprotein in rat brain microvessel endothelial cells via an insulin receptor-mediated PKC/NF-kappa B pathway but not a PI3K/Akt pathway[J].Eur J Pharmacol,2009,602(2-3):277–282.
[18]
Zhou SF.Structure,function and regulation of P-glycoprotein and its clinical relevance in drug disposition[J].Xenobiotica,2008,38(7-8):802–832.
[19]
Gulati A,Gerk PM. Role of placental ATP-binding cassette (ABC) transporters in antiretroviral therapy during pregnancy[J].J Pharm Sci,2009,98(7):2317–2335.
[20]
Zhou K,Zhou R,Zhu Q,et al.Evaluation of therapeutic effect and cytokine change during transplacental Digoxin treatment for fetal heart failure associated with fetal tachycardia,a case-control study[J].Int J Cardiol,2013,169(4):e62–e64.
[21]
Zhou KY,Hua YM,Zhu Q. Transplacental digoxin therapy for fetal atrial flutter with hydrops fetalis[J]. World J Pediatr,2012,8(3):275–277.
[22]
Lankas GR,Wise LD,Cartwright ME,et al. Placental P-glycoprotein deficiency enhances susceptibility to chemically induced birth defects in mice[J].Reprod Toxicol,1998,12(4):457–463.
[23]
Wang C,Xie L,Zhou K,et al.Increased risk for congenital heart defects in children carrying the ABCB1 Gene C3435T polymorphism and maternal periconceptional toxicants exposure[J].PLoS One,2013,8(7):e68807.
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