El Maradny E, Kanayama N, Halim A, Maehara K, Sumimoto K, Terao T
Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Handa-cho, 431-31 Hamamatsu, Japan.
Hum Reprod. 1996 May;11(5):1099-104. doi: 10.1093/oxfordjournals.humrep.a019304.
The aim of this research was to study and compare the mechanism of action of interleukin (IL)-8, IL-1beta dehydroepiandrosterone sulphate (DHEA-S) and prostaglandin (PG)E2 on the cervix. Five equal groups of pregnant rabbits (n = 45) were tested by either placebo or tested drugs in the form of vaginal suppositories once daily for 3 days. The suppositories contained human recombinant IL-8 (100 ng), IL-1beta (200 ng), DHEA-S (10 mg) or PGE2 (1 mg). All rabbits were tested by one dose, two doses or three doses. Consistency, dilatation and water contents were estimated 24 h after the last dose of treatment. Leukocyte infiltration of the cervices was studied after staining the cervical tissue sections with antirabbit RT2 monoclonal antibodies. Relative collagen concentration was assessed after staining with Picrosirius Red. Collagenase, gelatinase and elastase activities were measured in 100 mg of homogenized cervical connective tissue. Water contents were significantly increased in all tested cervices. Neutrophil numbers were increased in IL-8 and IL-1beta groups after the second dose of treatment (P < 0.0005 and 0.001 respectively). In the PGE2 group, neutrophils were increased after the third dose of treatment, whereas in DHEA-S group no significant changes were observed. Collagen content was significantly decreased in IL-8, IL-1beta and PGE2 groups after the first dose of treatment (P < 0.004, and 0.005 and 0.03 respectively). In the DHEA-S group, the decrease in collagen content occurred after the third dose (P < 0.05). Collagenase activity was markedly increased in IL-8, IL-1, and DHEA-S groups after the second dose of treatment (P < 0.001, 0.003 and 0.007 respectively). No significant increase in collagenase activity was found in PGE2 group. Gelatinase activity was significantly increased in IL-8, IL-1beta, PGE2 and DHEA-S groups after the second dose of treatment (P < 0.008, 0.01, 0.003 and 0.05 respectively). Also, elastase activity was increased after the second dose of treatment in all groups (P < 0.001, 0.001, 0.001 and 0.006 respectively). Our data suggest that ripening of the cervix in rabbit can be initiated by different mechanisms. Cytokines play a vital role in cervical ripening, especially IL-8 and IL-1. IL-8 is one of the factors which could ripen the cervix in a manner similar to the physiological process at term.
本研究旨在探讨和比较白细胞介素（IL）-8、IL-1β、硫酸脱氢表雄酮（DHEA-S）和前列腺素（PG）E2对子宫颈的作用机制。将45只妊娠兔平均分为五组，每天一次经阴道栓剂给予安慰剂或受试药物，共给药3天。栓剂含重组人IL-8（100 ng）、IL-1β（200 ng）、DHEA-S（10 mg）或PGE2（1 mg）。所有兔子分别接受一剂、两剂或三剂药物处理。在最后一剂处理24小时后评估子宫颈的硬度、扩张度和含水量。用抗兔RT2单克隆抗体对子宫颈组织切片染色后研究子宫颈的白细胞浸润情况。用天狼星红染色后评估相对胶原浓度。在100 mg匀浆的子宫颈结缔组织中测定胶原酶、明胶酶和弹性蛋白酶活性。所有受试子宫颈的含水量均显著增加。在给予第二剂处理后，IL-8组和IL-1β组的中性粒细胞数量增加（分别为P < 0.0005和0.001）。在PGE2组，给予第三剂处理后中性粒细胞增加，而在DHEA-S组未观察到显著变化。在给予第一剂处理后，IL-8组、IL-1β组和PGE2组的胶原含量显著降低（分别为P < 0.004、0.005和0.03）。在DHEA-S组，胶原含量在给予第三剂后降低（P < 0.05）。在给予第二剂处理后，IL-8组、IL-1组和DHEA-S组的胶原酶活性显著增加（分别为P < 0.001、0.003和0.007）。PGE2组未发现胶原酶活性显著增加。在给予第二剂处理后，IL-8组、IL-1β组、PGE2组和DHEA-S组的明胶酶活性显著增加（分别为P < 0.008、0.01、0.003和0.05）。此外，在给予第二剂处理后所有组的弹性蛋白酶活性均增加（分别为P < 0.001、0.001、0.001和0.006）。我们的数据表明，兔子宫颈成熟可通过不同机制启动。细胞因子在子宫颈成熟中起关键作用，尤其是IL-8和IL-1。IL-8是可使子宫颈成熟的因素之一，其作用方式类似于足月时的生理过程。
