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中华妇幼临床医学杂志(电子版) ›› 2017, Vol. 13 ›› Issue (01) : 71 -77. doi: 10.3877/cma.j.issn.1673-5250.2017.01.013

所属专题: 文献

论著

糖酵解相关基因在妊娠期肝内胆汁淤积症患者胎盘组织内的变化
陈昀1, 邢爱耘1, 胡雅毅1,()   
  1. 1. 610041 成都,四川大学华西第二医院妇产科、出生缺陷与相关妇儿疾病教育部重点实验室
  • 收稿日期:2016-11-05 修回日期:2017-01-08 出版日期:2017-02-01
  • 通信作者: 胡雅毅

Changes of glycometabolic genes in placenta of intrahepatic cholestasis of pregnancy

Yun Chen1, Aiyun Xing1, Yayi Hu1,()   

  1. 1. Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2016-11-05 Revised:2017-01-08 Published:2017-02-01
  • Corresponding author: Yayi Hu
  • About author:
    Corresponding author: Hu Yayi, Email:
引用本文:

陈昀, 邢爱耘, 胡雅毅. 糖酵解相关基因在妊娠期肝内胆汁淤积症患者胎盘组织内的变化[J/OL]. 中华妇幼临床医学杂志(电子版), 2017, 13(01): 71-77.

Yun Chen, Aiyun Xing, Yayi Hu. Changes of glycometabolic genes in placenta of intrahepatic cholestasis of pregnancy[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2017, 13(01): 71-77.

目的

探讨糖酵解相关基因糖转运体(GLUT)1、磷酸甘油酸激酶(PGK)1、乳酸脱氢酶(LDHA)基因在妊娠期肝内胆汁淤积症(ICP)患者胎盘组织内的表达及其意义。

方法

按照数字表法,随机选择2015年6月至10月于四川大学华西第二医院产科行择期剖宫产分娩的40例产妇的胎盘组织为研究对象。按照是否合并ICP,将其分别纳入ICP组(n=20)和对照组(n=20)。2组产妇行剖宫产分娩待胎盘娩出后,立即收取胎盘母体面的中央绒毛区组织。采用实时聚合酶链式反应(RT-PCR)及Western印迹法分别检测胎盘组织中GLUT1、PGK1、LDHA mRNA及蛋白相对表达水平。采用链霉菌抗生物素蛋白-过氧化物酶连结(SP)法进行免疫组化染色,并检测GLUT1、PGK1及LDHA在胎盘组织的定位。2组产妇的年龄、孕龄、孕次、产次、新生儿出生体重、娩出胎盘重量等一般临床资料比较,差异无统计学意义(P>0.05)。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

①2组胎盘组织中GLUT1、PGK1及LDHA mRNA表达水平比较,差异均无统计学意义(P>0.05)。②ICP组胎盘组织中GLUT1、PGK1及LDHA蛋白水平均高于对照组,并且差异有统计学意义(t=3.270,P=0.003;t=4.222,P<0.001;t=3.585,P=0.002)。③2组胎盘组织的合体滋养细胞及细胞滋养细胞的细胞质内均可见GLUT1、PGK1及LDHA蛋白的表达。

结论

ICP患者胎盘组织的糖酵解相关基因蛋白表达水平增高,糖酵解水平较正常晚孕期产妇代偿性增高,一定程度上可以缓解宫内低氧或缺氧,进一步加重的缺氧则可能导致组织能量代谢失代偿,从而导致胎死宫内等不良妊娠结局。

Objective

To investigate the expression of glucose transporter (GLUT1), phosphoglycerate kinase(PGK1) and lactate dehydrogenase (LDHA) in placentas of women with intrahepatic cholestasis of pregnancy (ICP).

Methods

From June to October, 2014, a total of 20 samples of placentas from women with ICP were included as the study group, and another 20 samples of normal placentas were selected as control group according to random number table. The relative expression levels of GLUT1 mRNA, PGK1 mRNA and LDHA mRNA were measured by real-time polymerase chain reaction (RT-PCR), and the relative protein levels of GLUT1, PGK1, LDHA were detected by Western blotting assay and immunohistological analysis. There were no significant differences between two groups in age, gestational age, gravidity, parity, birth weight of newborns and placental weight (P>0.05). 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 the parents of each participating patients.

Results

① There were no statistically significant difference between two groups in the relative expression levels of GLUT1 mRNA, PGK1 mRNA and LDHA mRNA (P>0.05). ② The relative protein levels of GLUT1, PGK1 and LDHA in control group were statistically lower than those in ICP group, which with significant difference (t=3.270, P=0.003; t=4.222, P<0.001; t=3.585, P=0.002). ③ All the proteins including GLUT1, PGK1 and LDHA were detected in the cytoplasma of cytotrophoblast and syncytiotrophoblast.

Conclusions

Under hypoxic conditions in pregnant women with ICP, the increased level of glycolysis may play a role in negative pregnancy outcomes.

表1 2组产妇胎盘组织中GLUT1、PGK1及LDHA mRNA相对表达水平比较(±s)
表2 2组产妇胎盘组织中GLUT1、PGK1及LDHA蛋白相对表达水平比较(±s)
图1 2组胎盘组织中GLUT1、PGK1及LDHA蛋白相对表达水平
图2 2组胎盘组织中GLUT1、PGK1及LDHA蛋白在细胞内的表达定位(图2A、2B:GLUT1蛋白;图2C、2D:PGK1蛋白;图2E、2F:LDHA蛋白)(SP染色,高倍镜)
[1]
Abedin P, Weaver JB, Egginton E. Intrahepatic cholestasis of pregnancy: prevalence and ethnic distribution[J]. Ethn Health, 1999, 4(1-2): 35-37.
[2]
Luo XL, Zhang WY. Obstetrical disease spectrum in China: an epidemiological study of 111,767 cases in 2011[J]. Chin Med J (Engl), 2015, 128(9): 1137-1146.
[3]
王莉,叶晓秀.妊娠期肝内胆汁淤积症与围生儿结局关系的研究进展[J].中华妇幼临床医学杂志(电子版),2015,9(5): 666-670.
[4]
Wikström Shemer E, Marschall HU, Ludvigsson JF, et al. Intrahepatic cholestasis of pregnancy and associated adverse pregnancy and fetal outcomes: a 12-year population-based cohort study[J]. BJOG, 2013, 120(6): 717-723.
[5]
Zhou B, Wang CH, Ding RB, et al. The relationship between the internal oxidation-reduction system and fetal distress on pregnant patients with intrahepatic cholestasis[J]. European Rev Med Pharmacol Sci, 2015, 19(20): 3817-3821.
[6]
Kim JW, Tchernyshyov I, Semenza GL, et al. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia[J]. Cell Metab, 2006, 3(3): 177-185.
[7]
Papandreou I, Cairns RA, Fontana L, et al. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption[J]. Cell Metab, 2006, 3(3): 187-197.
[8]
Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system[J]. Nat Med, 2003, 9(6): 677-684.
[9]
曹泽毅,主编.中华妇产科. 2版[M]. 北京:人民卫生出版社,2004:468-475.
[10]
Reid R, Ivey KJ, Rencoret RH, et al. Fetal complications of obstetric cholestasis[J]. Br Med J, 1976, 1(6014): 870-872.
[11]
王晓东,刘淑云,衡正昌. 妊娠肝内胆汁淤积症胎儿宫内缺氧机理的初步探讨[J]. 中华妇产科杂志,1998,33(2): 68-70.
[12]
贺晶,陈璐,梁琤.妊娠期肝内胆汁淤积症发生死胎的临床因素分析[J].中华妇产科杂志,2011,46(5): 333-337.
[13]
Lammert F, Marschall HU, Glantz A, et al. Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management[J]. J Hepatol, 2000, 33(6): 1012-1021.
[14]
Fisk NM, Storey GN. Fetal outcome in obstetric cholestasis[J]. Br J Obstet Gynaecol, 1988, 95(11): 1137-1143.
[15]
Sepúlveda WH, González C, Cruz MA, et al. Vasoconstrictive effect of bile acids on isolated human placental chorionic veins[J]. Eur J Obstet Gynecol Reprod Biol, 1991, 42(3): 211-215.
[16]
Wikström Shemer E, Thorsell M, Östlund E, et al. Stereological assessment of placental morphology in intrahepatic cholestasis of pregnancy[J]. Placenta, 2012, 33(11): 914-918.
[17]
Perez MJ, Velasco E, Monte MJ, et al. Maternal ethanol consumption during pregnancy enhances bile acid-induced oxidative stress and apoptosis in fetal rat liver[J]. Toxicology, 2006, 225(2-3): 183-194.
[18]
胡雅毅,王晓东,刘淑芸. 急性缺氧对妊娠期肝内胆汁淤积症患者胎盘组织HIF-1α表达的影响及与P53相关性的研究[J]. 四川大学学报(医学版),2006,37(6): 901-903.
[19]
Tal R. The role of hypoxia and hypoxia-inducible factor-1alpha in preeclampsia pathogenesis[J]. Biol Reprod, 2012, 87(6): 134.
[20]
Hayashi M, Sakata M, Takeda T, et al. Induction of glucose transporter 1 expression through hypoxia-inducible factor 1alpha under hypoxic conditions in trophoblast-derived cells[J]. J Endocrinol, 2004, 183(1): 145-154.
[21]
Wagegg M, Gaber T, Lohanatha FL, et al. Hypoxia promotes osteogenesis but suppresses adipogenesis of human mesenchymal stromal cells in a hypoxia-inducible factor-1 dependent manner[J]. PLoS One, 2012, 7(9): e46483.
[22]
Barros LF, Yudilevich DL, Jarvis SM, et al. Quantitation and immunolocalization of glucose transporters in the human placenta[J]. Placenta, 1995, 16(7): 623-633.
[23]
胡雅毅,刘淑芸,王晓东,等. 妊娠肝内胆汁淤积症患者胎盘组织缺氧及复氧时缺氧诱导因子1α表达水平的变化[J]. 中华妇产科杂志,2007,42(1): 54-56.
[24]
Kimura H, Weisz A, Kurashima Y, et al. Hypoxia response elements of the human vascular endothelial grown factor gene mediate transcriptional regulation by nitricoxide:control of hypoxia inducible factor 1α activity by nitricoxide[J]. Hemost Thrombs Vascul Biol, 2000, 95(1): 189-197.
[25]
Rajakumar A, Conrad KP. Expression, ontogeny, and regulation of hypoxia-inducible transcription factors in the human placenta[J]. Biol Reprod, 2000, 63(2): 559-569.
[26]
Huang LE, Arany Z, Livingston DM, et al. Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its alpha subunit[J]. J Biol Chem, 1996, 271(50): 32253-32259.
[27]
Semenza GL. Oxygen homeostasis[J]. Wiley Interdiscip Rev Syst Biol Med, 2010, 2(3): 336-361.
[28]
Wei W, Hu YY. Expression of hypoxia-regulated genes and glycometabolic genes in placenta from patients with intrahepatic cholestasis of pregnancy[J]. Placenta, 2014, 35(9): 732-736.
[29]
丁依玲,唐玲玲.妊娠肝内胆汁淤积症患者胎盘合体滋养细胞超微结构的观察与脐静脉血总胆酸水平的测定[J].中华妇产科杂志,2005,40(7): 453-456.
[30]
张耀,刘淑芸,王晓东.妊娠肝内胆汁淤积症胆汁酸水平及羊水胎粪污染与胎儿宫内缺氧的关系[J].中国综合临床,2003,19(6): 568-569.
[31]
刘伯宁,沈宁,陶雯琪,等.妊娠期肝内胆汁淤积症胎盘的组织计量测定[J].中华妇产科杂志,1988,23(1): 9-12.
[32]
胡雅毅,刘淑芸,杨开选.急性缺氧对妊娠期肝内胆汁淤积症患者胎盘绒毛超微结构的影响[J].华西医学,2006,21(4): 741-743.
[33]
Williamson C, Gorelik J, Eaton BM, et al. The bile acid taurocholate impairs rat cardiomyocyte function: a proposed mechanism for intra-uterine fetal death in obstetric cholestasis[J]. Clin Sci (Lond), 2001, 100(4): 363-369.
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