IL-6、STAT3在妊娠期肝内胆汁淤积症产妇胎盘组织中的表达及意义
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摘要
目的研究白细胞介素6(IL-6)和信号传导与转录激活因子3(STAT3)在妊娠期肝内胆汁淤积症(ICP)产妇胎盘组织中的表达及二者间的关系。方法选取2016年1月～2017年12月于广西科技大学附属柳州市人民医院(以下简称"我院")产科门诊产检并住院分娩的ICP产妇50例(ICP组),其中重度ICP组25例,轻度ICP组25例;同时取同期于我院分娩的健康产妇30名为对照组,搜集其胎盘组织采用免疫组织化学法检测IL-6及STAT3的表达。结果 ICP组孕妇胎盘滋养细胞中IL-6和STAT3阳性表达率明显高于对照组,差异有高度统计学意义(P <0.01),而在ICP轻度组和ICP重度组中两者阳性表达率比较,差异无统计学意义(P> 0.05);IL-6和STAT3在对照组、ICP轻度组、ICP重度组产妇胎盘滋养细胞中的阳性表达率呈递增趋势;ICP组IL-6与STAT3蛋白的表达呈正相关(r=0.694,P <0.01)。结论 IL-6及STAT3信号通路表达水平与ICP发病程度呈正相关,可作为联合诊断和病情评估的重要指标。
Objective To study the expression and the correlations of interleukin-6(IL-6) and signal transducer and activator transcription 3(STAT3) in the placentas of pregnant women with intrahepatic cholestasis of pregnancy(ICP).Methods A total of 50 pregnant women with ICP and in Obstetrics Clinic of Liuzhou General Hospital Attached to Guangxi University of Technology("our hospital" for short) from January 2016 to December 2017 was selected as ICP group, including 25 cases of mild ICP group, 25 cases of severe ICP group. At the same time, 30 healthy pregnant women taking prenatal examination in our hospital at the same period were selected in control group. Placentas of the above gravidas were collected and the expression and localization of IL-6 and STAT3 were determined via immunohistochemistry. Results The IL-6 and STAT3 positive cell rate of ICP group were significantly higher than those of control group, the differences were statistically significant(P < 0.01). There were no significant differences in positive cell rate between mild ICP group and severe ICP group(P > 0.05). The positive expression rate of IL-6 and STAT3 were gradually increased in placental trophoblast among the control group, mild ICP group and the severe ICP group. There were positive relations between IL-6 and STAT3 expression in ICP group(r = 0.694, P < 0.01). Conclusion The expression levels of IL-6 and STAT3 are positively correlated with the disease of ICP, which therefore might be used as combined diagnosis and evaluation of the state disease.
Objective To study the expression and the correlations of interleukin-6(IL-6) and signal transducer and activator transcription 3(STAT3) in the placentas of pregnant women with intrahepatic cholestasis of pregnancy(ICP).Methods A total of 50 pregnant women with ICP and in Obstetrics Clinic of Liuzhou General Hospital Attached to Guangxi University of Technology("our hospital" for short) from January 2016 to December 2017 was selected as ICP group, including 25 cases of mild ICP group, 25 cases of severe ICP group. At the same time, 30 healthy pregnant women taking prenatal examination in our hospital at the same period were selected in control group. Placentas of the above gravidas were collected and the expression and localization of IL-6 and STAT3 were determined via immunohistochemistry. Results The IL-6 and STAT3 positive cell rate of ICP group were significantly higher than those of control group, the differences were statistically significant(P < 0.01). There were no significant differences in positive cell rate between mild ICP group and severe ICP group(P > 0.05). The positive expression rate of IL-6 and STAT3 were gradually increased in placental trophoblast among the control group, mild ICP group and the severe ICP group. There were positive relations between IL-6 and STAT3 expression in ICP group(r = 0.694, P < 0.01). Conclusion The expression levels of IL-6 and STAT3 are positively correlated with the disease of ICP, which therefore might be used as combined diagnosis and evaluation of the state disease.
引文
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[11]黄鹰.TNF-α在妊娠期肝内胆汁淤积症中表达的研究[J].重庆医学,2015,44(14):1913-1915.
[12]殷震惠,杨华.VEGF、JAK2/STAT3信号通路与妇科疾病的关系[J].国际妇产科学杂志,2016,43(6):708-712.
[13]Fitzgerald JS,Germeyer A,Huppertz B,et al. Governing the invasive trophoblast:current aspects on intra-and extracellular regulation[J]. Am J Reprod Immunol,2010,63(6):492-505.
[14]Knofler M. Critical growth factors and signalling pathways controlling human trophoblast invasion[J]. Int J Dev Biol,2010,54(2-3):269-280.
[15]谭桢,刘爱明,罗敏,等.茵栀黄注射液抗胆汁淤积药效成分的筛选及其作用机制研究[J].中国中药杂志,2016,41(6):1113-1118.
[16]郭红梅,王建设.炎症在胆汁淤积中的作用[J].肝脏,2012,17(8):574-576.
[17]Wang Y,Levy DE. Comparative evolutionary genomics of the STAT family of transcription factors[J]. JAK STAT,2012,1(1):23-33.
[18]Rawlings JS,Rosler KM,Harrison DA. The JAK/STAT signaling pathway[J]. J Cell Sci,2004,117(8):1281-1283.
[19]Siveen KS,Sikka S,Surana R,et al. Targeting the STAT3signaling pathway in cancer:role of synthetic and natural inhibitors[J]. Biochim Biophys Acta,2014,1845(2):136-154.
[20]王斯南,曹海龙,许梦雀,等.白细胞介素6/信号转导和转录激活因子3通路在胆酸诱导Apcmin/+小鼠肠腺瘤癌变中的作用[J].中华消化杂志,2017,37(2):101-105.
[2]中华医学会妇产科学分会产科学组.妊娠期肝内胆汁淤积症诊疗指南(2015)[J].中华妇产科杂志,2015,31(10):1575-1578.
[3]黄婷,罗红霞,邵勇.妊娠期肝内胆汁淤积症胎盘合体滋养细胞中白细胞介素18和半胱氨酸天冬氨酸蛋白酶-1表达及其意义[J].中国实用妇科与产科杂志,2013,29(4):279-283.
[4]Bull LN,Hu D,Shah S,et al. Intrahepatic Cholestasis of Pregnancy(ICP)in U.S. Latinas and Chileans:Clinical features,Ancestry Analysis, and Admixture Mapping[J].PLoS One,2015,10(6):e0131211.
[5]蔡艾杞,刘路遥,张应凤,等.妊娠期肝内胆汁淤积症的研究进展[J].现代妇产科进展,2016,25(11):871-873.
[6]漆洪波,刘兴会.对新版“妊娠期肝内胆汁淤积症诊疗指南(2015)”的评价和进一步解释[J].中华妇产科杂志,2015,50(7):486-488.
[7]陈学海,漆洪波.妊娠期肝内胆汁淤积症相关问题[J].中国实用妇科与产科杂志,2015,31(12):1100-1102.
[8]Liu Y,Lin J. Blocking the IL-6-STAT3 signaling pathway:potential liver cancer therapy[J]. Future Oncol,2011,7(2):161-164.
[9]方彩云,方孝梅,赵亚娟.妊娠肝内胆汁淤积症患者血清中s VCAM-1及IL-6临床检测意义[J].中国计划生育学杂志,2008,148(2):106-108.
[10]El-Faramawy AA,El-Shazly LB,Abbass AA,et al. Serum IL-6 and IL-8 in infants with biliary atresia in comparison to intrahepatic cholestasis[J]. Trop Gastroenterol,2011,32(1):50-55.
[11]黄鹰.TNF-α在妊娠期肝内胆汁淤积症中表达的研究[J].重庆医学,2015,44(14):1913-1915.
[12]殷震惠,杨华.VEGF、JAK2/STAT3信号通路与妇科疾病的关系[J].国际妇产科学杂志,2016,43(6):708-712.
[13]Fitzgerald JS,Germeyer A,Huppertz B,et al. Governing the invasive trophoblast:current aspects on intra-and extracellular regulation[J]. Am J Reprod Immunol,2010,63(6):492-505.
[14]Knofler M. Critical growth factors and signalling pathways controlling human trophoblast invasion[J]. Int J Dev Biol,2010,54(2-3):269-280.
[15]谭桢,刘爱明,罗敏,等.茵栀黄注射液抗胆汁淤积药效成分的筛选及其作用机制研究[J].中国中药杂志,2016,41(6):1113-1118.
[16]郭红梅,王建设.炎症在胆汁淤积中的作用[J].肝脏,2012,17(8):574-576.
[17]Wang Y,Levy DE. Comparative evolutionary genomics of the STAT family of transcription factors[J]. JAK STAT,2012,1(1):23-33.
[18]Rawlings JS,Rosler KM,Harrison DA. The JAK/STAT signaling pathway[J]. J Cell Sci,2004,117(8):1281-1283.
[19]Siveen KS,Sikka S,Surana R,et al. Targeting the STAT3signaling pathway in cancer:role of synthetic and natural inhibitors[J]. Biochim Biophys Acta,2014,1845(2):136-154.
[20]王斯南,曹海龙,许梦雀,等.白细胞介素6/信号转导和转录激活因子3通路在胆酸诱导Apcmin/+小鼠肠腺瘤癌变中的作用[J].中华消化杂志,2017,37(2):101-105.