阿魏酸钠对脂多糖引起小鼠早产和死胎的防治作用（英文）

Protective effect of sodium ferulate against lipopolysaccharideinduced preterm delivery and intra-uterine fetal death in mice

目的研究阿魏酸钠(SF)对脂多糖导致早产和死胎的防治作用。方法昆明种孕小鼠妊娠10~15 d(GD10~GD15)每天sc给予SF 25或50 mg·kg^(-1),GD15.5 ip给予脂多糖(LPS)150μg·kg^(-1)造成早产及死胎模型,观察早产和死胎的发生率;利用HE染色,观察胎盘和子宫组织病理学变化;通过商用试剂盒测定母肝、胎盘和胎肝中硫代巴比妥酸反应产物(TBARS)及还原型谷胱甘肽(GSH)浓度含量、谷胱甘肽巯基转移酶(GST)及谷胱甘肽过氧化物酶(GSH-Px)活性;酶联免疫吸附测定羊水中白细胞介素1β(IL^(-1)β)和肿瘤坏死因子α(TNF-α)的水平。结果 LPS组早产发生率为47.8%,妊娠天数为(17.5±1.3)d,活胎率为42.6%;与之相比,SF50 mg·kg^(-1)可以显著降低LPS引起早产发生率(14.3%,P<0.01),延长妊娠时间〔(18.4±0.5)d,P<0.05〕,并提高活胎率(75.6%,P<0.01)。与LPS组相比,SF 50 mg·kg^(-1)具有逆转母肝和胎肝GSH降低的趋势;恢复胎盘GST活性〔(163±82)kU·g-1蛋白质vs(95±90)kU·g-1蛋白质,P<0.01〕以及胎肝TBARS的含量水平〔(2.5±0.4)μmol·g-1蛋白质vs(3.1±0.6)μmol·g-1蛋白质,P<0.01〕;降低羊水TNF-α表达水平〔(11±8)ng·L^(-1)vs(20±8)ng·L^(-1),P<0.01〕;抑制胎盘充血和子宫粒细胞浸润。结论 SF可以防治LPS导致的早产和死胎,其作用机制可能与抗氧化和抑制炎症有关。

OBJECTIVE To investigate the effect of sodium ferulate（SF） on lipopolysaccharide（LPS）-induced preterm delivery and intra-uterine fetal death（IUFD）. METHODS Pregnant Kunming mice were subcutaneously pretreated with SF（25 or 50 mg·kg（-1）） from gestational day（GD） 10 to GD15 and with the single injection of LPS（150 μg·kg（-1）, ip） on GD15.5. The incidence of preterm delivery and IUFD was observed. HE staining was used for uterine and placental histological evaluation. The levels of thiobarbituric acid reactive substances（TBARS） and reduced glutathione（GSH） as well as the activities of glutathione S-transferase（GST） and glutathione peroxidase（GSH-Px） were detected in the maternal liver, placenta, and fetal liver using commercial kits. Interleukin-1β（IL-（-1）β） and tumor necrosis factor-α（TNF-α） levels in amniotic fluid were evaluated by enzyme linked immunosorbent assay. RESULTS For LPS group, the incidence of preterm was 47.8%, delivery time was（17.5 ± 1.3） d,and the pups′ survival rate was only 42.6%. Compared with LPS-treated group, SF 50 mg · kg（-1）group showed a lower incidence of preterm（14.3%, P0.01）, longer gestational days（18.4 ± 0.5, P0.05）,and a higher pups′ survival rate（75.6%, P0.01）. SF 50 mg·kg（-1）restored the LPS-induced GSH both in the maternal and fatal liver（a tendency without statistical significance）, GST activity〔（163±82） kU ·g-（-1）protein vs（95±90） k U·g-1protein, P0.01）〕in the placenta, TBARS conten〔t（2.5±0.4） μmol·g-1protein vs（3.1±0.6） μmol·g-1protein, P0.01〕in the fetal liver, and TNF-α level〔（11±8） ng·L-（-1）vs（20±8） ng·L-（-1）, P0.01〕in the amniotic fluid. SF also attenuated LPS-induced placental congestion and neutrophil infiltration in the uterus. CONCLUSION SF may protect against LPS-induced preterm delivery and IUFD,and anti-oxidation as well as anti-inflammation may contribute to these effects.