Bry K, Hallman M
Department of Pediatrics, University of California, Irvine 92717.
Am J Obstet Gynecol. 1993 Apr;168(4):1318-22. doi: 10.1016/0002-9378(93)90388-y.
The purpose of the study was to determine whether preterm parturition in the rabbit can be induced by intraamniotic injection of proinflammatory cytokines, interleukin-1 alpha and tumor necrosis factor-alpha, and whether transforming growth factor-beta 2, an inhibitor of the cytokine-induced prostaglandin synthesis, modifies the effect of these cytokines.
New Zealand White rabbits were injected in each amniotic cavity on day 24 of gestation with one of the following: a combination of interleukin-1 alpha (150 ng) and tumor necrosis factor-alpha (1.25 micrograms), 50 ng of transforming growth factor-beta 2 concomitantly with interleukin-1 alpha and tumor necrosis factor-alpha, or vehicle. In the first study the animals were observed for signs of delivery until day 29 of gestation. In the second study the effect of transforming growth factor-beta 2 (50 ng/fetus) on the rate of premature delivery was evaluated. In the third study the concentrations of prostaglandin E2 and 13,14-dihydro-15-keto-prostaglandin F2 alpha were measured in the amniotic fluid on day 27 of gestation. The statistics used were Fisher's exact test, the chi 2 test, and the Mann-Whitney U test.
Altogether 61 of 191 fetuses (32%) were born prematurely in the interleukin-1 alpha-tumor necrosis factor-alpha group, whereas only two of 161 fetuses (1.2%) (p = 0.0001) and one of 159 (0.6%) (p = 0.0001) were born prematurely in the interleukin-1 alpha-tumor necrosis factor-alpha-transforming growth factor-beta 2 group and in the control group, respectively. Of the 23 animals injected with interleukin-1 alpha and tumor necrosis factor-alpha, six (26%) delivered all of their fetuses prematurely versus none in the other groups (p = 0.02). None of the 88 fetuses in the transforming growth factor-beta 2 group were born prematurely. The prostaglandin E2 concentrations in the amniotic fluids were higher in the interleukin-1 alpha-tumor necrosis factor-alpha group than in the interleukin-1 alpha-tumor necrosis factor-alpha-transforming growth factor-beta 2 group (p = 0.05) or in the control group (p = 0.02).
Preterm parturition can be provoked in the rabbit by intraamniotic injections of interleukin-1 alpha and tumor necrosis factor-alpha. Transforming growth factor-beta 2 prevents the cytokine-induced increase in premature delivery.
本研究旨在确定羊膜腔内注射促炎细胞因子白细胞介素 -1α 和肿瘤坏死因子 -α 是否能诱发兔早产，以及细胞因子诱导的前列腺素合成抑制剂转化生长因子 -β2 是否能改变这些细胞因子的作用。
在妊娠第24天，向新西兰白兔的每个羊膜腔内注射以下物质之一：白细胞介素 -1α（150 ng）和肿瘤坏死因子 -α（1.25微克）的组合、50 ng转化生长因子 -β2 与白细胞介素 -1α 和肿瘤坏死因子 -α 同时注射，或注射赋形剂。在第一项研究中，观察动物直至妊娠第29天的分娩迹象。在第二项研究中，评估转化生长因子 -β2（50 ng/胎儿）对早产率的影响。在第三项研究中，于妊娠第27天测量羊水中前列腺素E2和13,14 - 二氢 -15 - 酮 - 前列腺素F2α 的浓度。所使用的统计方法为Fisher精确检验、卡方检验和Mann - Whitney U检验。
在白细胞介素 -1α - 肿瘤坏死因子 -α 组中，191只胎儿中有61只（32%）早产，而在白细胞介素 -1α - 肿瘤坏死因子 -α - 转化生长因子 -β2 组和对照组中，161只胎儿中分别仅有2只（1.2%）（p = 0.0001）和159只中的1只（0.6%）（p = 0.0001）早产。在注射白细胞介素 -1α 和肿瘤坏死因子 -α 的23只动物中，有6只（26%）使其所有胎儿早产，而其他组均无此情况（p = 0.02）。转化生长因子 -β2 组的88只胎儿均未早产。白细胞介素 -1α - 肿瘤坏死因子 -α 组羊水中的前列腺素E2浓度高于白细胞介素 -1α - 肿瘤坏死因子 -α - 转化生长因子 -β2 组（p = 0.05）或对照组（p = 0.02）。
羊膜腔内注射白细胞介素 -1α 和肿瘤坏死因子 -α 可诱发兔早产。转化生长因子 -β2 可预防细胞因子诱导的早产增加。
