McLaren J, Taylor D J, Bell S C
Preterm Birth Research Group, Department of Obstetrics and Gynaecology, University of Leicester, United Kingdom.
Am J Obstet Gynecol. 2000 Feb;182(2):409-16. doi: 10.1016/s0002-9378(00)70232-8.
Regional structural alterations that develop before labor are important in the mechanisms of both physiologic and pathologic membrane rupture, because they are also detected in preterm prelabor rupture of the fetal membranes, the most common cause of preterm birth (as great as 60%). Matrix metalloproteinases are located in the fetal membranes and are the main mediators of extracellular matrix degradation. The objective of this study was to examine whether gelatinases (matrix metalloproteinases 2 and 9) could be involved in the development of these regional structural changes seen at term before labor.
Fetal membranes from patients undergoing elective cesarean delivery were regionally sampled from over the cervix (cervical membranes) and midway between this area and the placental edge (midzone). Fetal membranes obtained after spontaneous labor and delivery at term were also regionally sampled. Matrix metalloproteinase 2 and 9 activities were assessed by gelatin zymography, whereas total matrix metalloproteinase 9 protein was determined by enzyme-linked immunosorbent assay.
Zymography only detected activity corresponding to the pro-matrix metalloproteinase 2 (72 kd) and 9 (92 kd) forms in prelabor fetal membranes. Although the levels of pro-matrix metalloproteinase 2 showed no regional differences, the pro-matrix metalloproteinase 9 level was higher in the cervical area than in the midzone (2.5 +/- 0.98 vs 0.76 +/- 0.28 optical density units/20 microg protein; P <.01). The concentration of pro-matrix metalloproteinase 9 protein in the cervical area was also significantly higher than that in the midzone (6.69 +/- 4.8 vs 1.58 +/- 1.14 ng/mg protein; P <.01). After delivery both pro-matrix metalloproteinase 2 and 9 activities were elevated, whereas pro-matrix metalloproteinase 9 protein activity showed no regional difference between the rupture site and midzone (23.47 +/- 4.5 vs 25. 3 +/- 6.2 ng/mg protein). Active bands of matrix metalloproteinases 2 (66 kd) and 9 (83 kd) were also detected after delivery.
This study suggests that a specific regional induction of pro-matrix metalloproteinase 9 occurs in the cervical area before labor and may play a role in "programming" this area for subsequent rupture after activation during labor.
分娩前出现的局部结构改变在生理性和病理性胎膜破裂机制中均很重要，因为在胎膜早破（早产最常见的原因，高达60%）中也能检测到这些改变。基质金属蛋白酶位于胎膜中，是细胞外基质降解的主要介质。本研究的目的是检验明胶酶（基质金属蛋白酶2和9）是否参与足月分娩前所见的这些局部结构变化的发生过程。
对接受择期剖宫产的患者的胎膜，在宫颈上方（宫颈胎膜）以及该区域与胎盘边缘中间位置（中间区域）进行局部取样。对足月自然分娩后的胎膜也进行局部取样。通过明胶酶谱法评估基质金属蛋白酶2和9的活性，而通过酶联免疫吸附测定法测定总基质金属蛋白酶9蛋白。
酶谱法仅在分娩前胎膜中检测到与前基质金属蛋白酶2（72kd）和9（92kd）形式相对应的活性。尽管前基质金属蛋白酶2的水平无区域差异，但宫颈区域的前基质金属蛋白酶9水平高于中间区域（2.5±0.98对0.76±0.28光密度单位/20μg蛋白；P<.01）。宫颈区域前基质金属蛋白酶9蛋白的浓度也显著高于中间区域（6.69±4.8对1.58±1.14ng/mg蛋白；P<.01）。分娩后，前基质金属蛋白酶2和9的活性均升高，而前基质金属蛋白酶9蛋白活性在破裂部位和中间区域之间无区域差异（23.47±4.5对25.3±6.2ng/mg蛋白）。分娩后也检测到了基质金属蛋白酶2（66kd）和9（83kd）的活性条带。
本研究表明，分娩前宫颈区域会发生前基质金属蛋白酶9的特异性局部诱导，可能在分娩时激活后使该区域为后续破裂进行“预编程”中发挥作用。
