NF-κBp65、Lin28B和IL-6在不同临产状态孕妇外周血中的表达
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摘要
目的:探讨NF-κBp65、Lin28B和IL-6在早产和足月妊娠孕妇外周血中的表达情况,进一步明确其在分娩发动中的预测价值。方法:采集先兆早产组、早产临产组、足月临产组和正常妊娠组各25例孕妇的外周血血清,采用ELISA法检测并比较4组血清中NF-κBp65、IL-6、Lin28B的表达情况;同时将先兆早产组与早产临产组、临产组(包括早产临产组和足月临产组)与正常妊娠组NF-κBp65、IL-6、Lin28B表达水平行直线相关分析。结果:(1)NF-κBp65的表达水平在早产临产组中最高(13.99±0.72 ng/ml),IL-6的表达水平在早产临产组中最高(54.34±6.66 pg/ml),Lin28B的表达水平在正常妊娠组中最高(10.67±0.52 ng/ml),经LSD-t检验,4组中NF-κBp65、IL-6及Lin28B的表达水平两两间比较,差异均有统计学意义(P<0.05)。(2)先兆早产组和早产临产组中NF-κBp65与IL-6的表达均呈正相关(r=0.557,P<0.05;r=0.587,P<0.05),NF-κBp65与Lin28B的表达及IL-6与Lin28B的表达均无相关性(P>0.05)。(3)临产组中NF-κBp65与IL-6的表达呈高度正相关(r=0.899,P<0.05),NF-κBp65与Lin28B的表达呈高度负相关(r=-0.863,P<0.05);IL-6表达水平与Lin28B的表达呈高度负相关(r=-0.798,P<0.05)。结论:IL-6和NF-κBp65对早产临产具一定预测价值;Lin28B与胎儿成熟程度相关,对早产无预测价值。
Objective:The aim of this study was to investigate the levels of nuclear factor kappa Bp65(NF-κBp65),Lin28B and Interleukin 6(IL-6) from maternal peripheral blood of different pregnant groups and to assess their values for prediction of preterm labor.Methods:According to the cervix opening examination,100 pregnant women were divided into threatened preterm group(n = 25),preterm labor(n = 25),term vaginal delivery(n = 25),and normal term pregnant group(n = 25).ELISA were adopted to test the expression levels of NF-κBp65,Lin28B and IL-6 in 4 groups,and linear correlation analysis was adopted toanalyze the correlation of the levels of NF-κBp65,IL-6 and Lin28B between the threatened preterm group and preterm labor group,the relation of the levels between labor group(including premature labor and term labor) and normal pregnancy group.Results:(1)The level of NF-κBp65 expression of preterm labor group was the highest in four groups(13.99±0.72 ng/ml),IL-6 expression of preterm labor group was the highest in four groups(54.34±6.66 pg/ml).And Lin28B expression of normal term pregnant group was the highest in four groups(10.67 ± 0.52 ng/ml).According to LSD-t test and multiple comparison,there was significant difference on the the levels of NF-κBp65,IL-6 and Lin28B among the four groups(P<0.05).(2)The linear correlation between levels of NF-κBp65 and IL-6 of threatened preterm group and preterm labor was positive correlation(r = 0.557,P<0.05;r = 0.587,P<0.05),but there was no linear correlation between levels of NF-κBp65 and Lin28B(P > 0.05),there was no linear correlation between levels of IL-6 and Lin28B(P>0.05).(3)In the labor group,the expression level of NF-κBp65 was positively correlated with the expression level of IL-6(r = 0.899,P < 0.05),and was negatively correlated with the expression level of Lin28B(r=-0.863,P<0.05).The expression level of IL-6 was negatively correlated with the expression level of Lin28B(r=-0.798,P<0.05).Conclusions:IL-6 and NF-κBp65 have a certain predictive value for preterm labor.Lin28B is associated with fetal maturity and has no predictive value for preterm labor.
Objective:The aim of this study was to investigate the levels of nuclear factor kappa Bp65(NF-κBp65),Lin28B and Interleukin 6(IL-6) from maternal peripheral blood of different pregnant groups and to assess their values for prediction of preterm labor.Methods:According to the cervix opening examination,100 pregnant women were divided into threatened preterm group(n = 25),preterm labor(n = 25),term vaginal delivery(n = 25),and normal term pregnant group(n = 25).ELISA were adopted to test the expression levels of NF-κBp65,Lin28B and IL-6 in 4 groups,and linear correlation analysis was adopted toanalyze the correlation of the levels of NF-κBp65,IL-6 and Lin28B between the threatened preterm group and preterm labor group,the relation of the levels between labor group(including premature labor and term labor) and normal pregnancy group.Results:(1)The level of NF-κBp65 expression of preterm labor group was the highest in four groups(13.99±0.72 ng/ml),IL-6 expression of preterm labor group was the highest in four groups(54.34±6.66 pg/ml).And Lin28B expression of normal term pregnant group was the highest in four groups(10.67 ± 0.52 ng/ml).According to LSD-t test and multiple comparison,there was significant difference on the the levels of NF-κBp65,IL-6 and Lin28B among the four groups(P<0.05).(2)The linear correlation between levels of NF-κBp65 and IL-6 of threatened preterm group and preterm labor was positive correlation(r = 0.557,P<0.05;r = 0.587,P<0.05),but there was no linear correlation between levels of NF-κBp65 and Lin28B(P > 0.05),there was no linear correlation between levels of IL-6 and Lin28B(P>0.05).(3)In the labor group,the expression level of NF-κBp65 was positively correlated with the expression level of IL-6(r = 0.899,P < 0.05),and was negatively correlated with the expression level of Lin28B(r=-0.863,P<0.05).The expression level of IL-6 was negatively correlated with the expression level of Lin28B(r=-0.798,P<0.05).Conclusions:IL-6 and NF-κBp65 have a certain predictive value for preterm labor.Lin28B is associated with fetal maturity and has no predictive value for preterm labor.
引文
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[10]Lappas M.Nuclear factor-κB mediates placental growth factor induced pro-labor mediators in human placenta[J].Mol Hum Reprod,2012,18(7):354-361.
[11]张卫社,周昌菊,吴新华,等.孕妇外周血中C反应蛋白和白细胞介素6在亚临床感染性早产预测中的价值[J].中华妇产科杂志,2007,42(1):56-58.
[12]Viswanathan SR,Daley GQ.Lin28:a micro RNA regulator with a macro role[J].Cell,2010,140(4):445-449.
[13]Zhu H,Shyh-Chang N,SegrèAV,et al.The Lin28/let-7 axis regulates glucose metabolism[J].Cell,2011,147(1):81-94.
[14]Lozoya T,Domínguez F,Romero-Ruiz A,et al.The Lin28/Let-7 system in early human embryonic tissue and ectopic pregnancy[J].PLo S One,2014,9(1):e87698.
[15]Lappas M.RAF1 is increased in laboring myometrium and modulates inflammation-induced pro-labor mediators[J].Reproduction,2016,151(4):411-420.
[16]Keelan JA,Khan S,Yosaatmadia F,et al.Prevention of inflammatory activation of human gestational membranes in an ex vivo model using a pharmacological NF-κB inhabitor[J].J Immunol,2009,183(8):5270-5278.
[2]Lappas M.The adaptor protein p62 mediates nuclear factorκB activation in response to inflammation and faciliates the formation of prolabor mediators in human myometrium[J].Reprod Sci,2017,24(5):762-772.
[3]马薇.RNA结合蛋白Lin28在生殖细胞发育和性成熟过程中的作用[J].生殖与避孕,2013,33(3):193-198.
[4]Iliopoulos D,Hirsch HA,Struhl K.An epigenetic switch involving NF-kappa B,Lin28,let-7 micro RNA,and IL-6 links inflammation to cell transformation[J].Cell,2009,139(4):693-706.
[5]马薇.人子宫体部平滑肌收缩相关蛋白的筛选[J].中南大学学报(医学版),2013,38(10):1042-1050.
[6]Deguchi A,Tomita T,Ohto U,et al.Eritoran inhibits S100 A8-mediated TLR4/MD-2 activation and tumor growth by changing the immune microenvironment[J].Oncogene,2016,35(11):1445-1456.
[7]Gary Cunningham F,Leveno KJ,Bloom S,et al.Williams Obstetrics[M].24thEdition:Mc Graw-Hill Education,2014:829-861.
[8]李康,贺佳主编.医学统计学[M].6版.北京:人民卫生出版社,2013:111.
[9]Lappas M,Rice GE.The role and regulation of the nuclear factor kappa B signaling pathway in human labour[J].Placenta,2007,28(5-6):543-556.
[10]Lappas M.Nuclear factor-κB mediates placental growth factor induced pro-labor mediators in human placenta[J].Mol Hum Reprod,2012,18(7):354-361.
[11]张卫社,周昌菊,吴新华,等.孕妇外周血中C反应蛋白和白细胞介素6在亚临床感染性早产预测中的价值[J].中华妇产科杂志,2007,42(1):56-58.
[12]Viswanathan SR,Daley GQ.Lin28:a micro RNA regulator with a macro role[J].Cell,2010,140(4):445-449.
[13]Zhu H,Shyh-Chang N,SegrèAV,et al.The Lin28/let-7 axis regulates glucose metabolism[J].Cell,2011,147(1):81-94.
[14]Lozoya T,Domínguez F,Romero-Ruiz A,et al.The Lin28/Let-7 system in early human embryonic tissue and ectopic pregnancy[J].PLo S One,2014,9(1):e87698.
[15]Lappas M.RAF1 is increased in laboring myometrium and modulates inflammation-induced pro-labor mediators[J].Reproduction,2016,151(4):411-420.
[16]Keelan JA,Khan S,Yosaatmadia F,et al.Prevention of inflammatory activation of human gestational membranes in an ex vivo model using a pharmacological NF-κB inhabitor[J].J Immunol,2009,183(8):5270-5278.