Kajikawa S, Kaga N, Futamura Y, Kakinuma C, Shibutani Y
Toxicology Laboratory, Mochida Pharmaceutical Co., Ltd., Fujieda, Shizuoka, Japan.
J Pharmacol Toxicol Methods. 1998 Apr;39(3):147-54. doi: 10.1016/s1056-8719(98)00015-x.
The purpose of this study was to determine whether or not lipoteichoic acid (LTA) could induce preterm delivery in mice. On days 15 and 17 of pregnancy, female C3H/HeN mice impregnated by male B6D2F1 mice were given intraperitoneal injections of LTA (12.5-75 mg/kg, single dose or repeated doses at a 3-h interval). We examined the changes in cervix, placental trophoblasts, and plasma and amniotic fluid concentrations of interleukin-1alpha (IL-1alpha), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) after dosing with LTA. In addition, the effect of LTA on the contraction of isolated uterine muscle from pregnant mice was also measured. The incidence of preterm delivery was highest (100%), when the pregnant animals were treated with 75 mg/kg LTA twice on day 15 of pregnancy or with 25 mg/kg LTA twice on day 17 of pregnancy. LTA-accelerated cervical ripening and placental abruption preceding the onset of preterm delivery, as well as increased plasma and amniotic fluid concentrations of IL-1alpha, IL-6, and TNF-alpha. Also, LTA increased contraction of uterine muscle strips. In conclusion, LTA induced preterm delivery in mice in the same manner as lipopolysaccharide (LPS), but the effective dose of LTA was larger than that of LPS.
本研究的目的是确定脂磷壁酸（LTA）是否能诱导小鼠早产。在妊娠第15天和第17天，用雄性B6D2F1小鼠使雌性C3H/HeN小鼠受孕后，给其腹腔注射LTA（12.5 - 75 mg/kg，单剂量或每隔3小时重复给药）。我们检测了给予LTA后宫颈、胎盘滋养层细胞以及血浆和羊水白细胞介素 - 1α（IL - 1α）、白细胞介素 - 6（IL - 6）和肿瘤坏死因子 - α（TNF - α）浓度的变化。此外，还检测了LTA对妊娠小鼠离体子宫肌收缩的影响。当妊娠动物在妊娠第15天接受两次75 mg/kg LTA治疗或在妊娠第17天接受两次25 mg/kg LTA治疗时，早产发生率最高（100%）。LTA加速了早产发作前的宫颈成熟和胎盘早剥，同时增加了血浆和羊水IL - 1α、IL - 6和TNF - α的浓度。此外，LTA增加了子宫肌条的收缩。总之，LTA以与脂多糖（LPS）相同的方式诱导小鼠早产，但LTA的有效剂量大于LPS。
