MMP-8、IL-6、IL-8水平与早产、胎膜早破关系的研究

MMP-8, IL-6 and IL-8 levels in preterm delivery and premature rupture of fetal membrane

目的探讨基质金属蛋白酶-8(MMP-8)、细胞因子IL-6、IL-8与早产、胎膜早破的关系。方法选择单胎初产妇100例作为研究对象,按孕周、胎膜是否破裂和产妇是否临产分为早产临产(PL)、未足月胎膜早破(PPROM)、足月胎膜早破(TPROM)、足月临产(TL)、足月未临产产妇组(对照组),共5组,每组各20例。用ELISA法检测孕妇羊水及血清中MMP-8及IL-6、IL-8的水平,用免疫组化法(SP)检测所有产妇子宫下段近宫颈处胎膜组织MMP-8的表达情况。结果(1)PL、PPROM、TPROM、TL组羊水MMP-8水平分别为(465.71±78.02)ng/ml、(474.12±65.08)ng/ml、(262.81±43.56)ng/ml、(203.46±46.94)ng/ml,均高于对照组(121.57±37.38)ng/m(l均P<0.05),PL、PPROM组高于TPROM、TL组(均P<0.05),各组血清MMP-8水平差异无统计学意义(P>0.05);(2)PL、PPROM、TPROM组血清和羊水中IL-6、IL-8水平均高于TL组和对照组(均P<0.05),PPROM组高于TPROM、PL组(均P<0.05);(3)PL、PPROM、TPROM、TL组子宫下段近宫颈处胎膜组织MMP-8表达的免疫组化积分高于对照组(均P<0.05);(4)PL、PPROM、TPROM组合并绒毛膜羊膜炎患者羊水中MMP-8和IL-6、IL-8水平明显高于非绒毛膜羊膜炎患者(均P<0.05);(5)羊水中MMP-8水平与血清、羊水中IL-6、IL-8水平呈正相关(r=0.798、0.793,均P<0.05);羊水MMP-8水平与MMP-8在胎膜上的表达呈正相关(r=0.662P<0.05)。结论(1)MMP-8、IL-6、IL-8与早产、胎膜早破密切相关;(2)羊水MMP-8和血清、羊水IL-6、IL-8的升高对诊断绒毛膜羊膜炎有临床应用价值,可作为早产、胎膜早破合并绒毛膜羊膜炎的诊断指标;(3)羊水中MMP-8、IL-6、IL-8的升高在早产、胎膜早破中起协同作用,细胞因子IL-6、IL-8通过诱导MMP的合成和活化,使羊水中MMP-8水平升高及胎膜MMP-8表达增加,导致早产、胎膜早破。

Objective To investigate blood and amniotic fluid levels of matrix metalloproteinases-8 （MMP-8） , interleukin-6 （IL-6） and interleukin-8 （IL-8） in preterm delivery and premature rupture of fetal membranes. Methods A cross-sectional study was conducted with 50 women in the following categories： （1） preterm delivery with intact membranes （PL, n=10）, （2） preterm delivery with premature rupture of membranes （PPROM, n=10）, （3） term delivery with premature rupture of membranes （TPROM, n=10）, （4） term in labor （TL, n=10）, （5） term not in labor （control group, n=10）. MMP-8, IL-6 and IL-8 levels in maternal serum and amniotic fluid were detected by enzyme-linked immunoabsorbent assay （ELISA）. The expressions of MMP-8 in the fetal membranes were examined by immunohistochemical assay （SP）. Results （1） The levels of MMP-8 in amniotic fluid were higher than those in the control group （P〈0.05）; there were no significant differences in serum MMP-8 levels among five groups （P〉0.05）;（2） The IL-6 and IL-8 levels in serum and amniotic fluid of PL, PPROM and TPROM groups were higher than those in TL group and control group （P〈0.05）; and those in the PPROM was the highest one among all groups （P〈O.05）; （3） Immunohistochemical score （IH score） of MMP-8 in the cervical fetal membranes were higher than that in control group （P〈0.05）; （4） The levels of MMP-8 in the amniotic fluid, IL-6, IL-8 in the amniotic fluid and serum in the chorioamnionitis were higher than those in non-chorioamnionitis among PL, PPROM and TPROM groups （P〈0.05） ; （5） The levels of MMP-8 in amniotic fluid were correlated with IL-6 in the serum and amniotic fluid （P〈0.05）; the levels of MMP-8 in the amniotic fluid were correlated with IL-8 in the serum and amniotic fluid （P〈0.05）, the levels of MMP-8 in the amniotic fluid were correlated with MMP-8 expression in the cervical fetal membranes （P〈0.05）. Conclusion Our study indicates that：（1 ）Premature delivery and rupture of fetal membranes （term and preterm） are associated with MMP-8 and IL-6, IL-8; （2） The levels of MMP-8 and IL-6 ,IL-8 in amniotic fluid and IL-6 ,IL-8 in serum are valuable clinical index for identifying the chorioamnionitis in patients with preterm and PROM ;（3） MMP-8 and IL-6, IL-8 in amniotic fluid may be involved in preterm and PROM; IL-6, IL-8 may induce the secretion and activation of MMP-8,upregulate the level of MMP-8 in the amniotic fluid and the expression in the cervical fetal membranes, which may result in the preterm labor and PROM.