摘要
目的研究低剂量细菌脂多糖(LPS)预处理对高剂量LPS诱导宫内胎儿死亡(IUFD)和早产的影响。方法实验1:孕鼠随机分为4组,LPS组和对照组分别于孕15 d腹腔注射LPS(120μg/kg)和等容积NS;LPS(4 h)+LPS组和LPS(24 h)+LPS组孕鼠分别在给予低剂量LPS(10μg/kg,i.p.)4、24 h后再腹腔注射高剂量LPS(120μg/kg)。高剂量LPS处理后密切观察各组孕鼠早产迹象,第18 d剖杀各组非早产孕鼠,记录活胎数、死胎数、吸收胎数和着床腺数。实验2:随机分成4组(同实验1)。每组12只孕鼠在高剂量LPS处理1.5 h后被剖杀,取孕鼠血清和羊水,并测定其肿瘤坏死因子α(TNF-α)和白细胞介素10(IL-10)含量;另外每组12只孕鼠于高剂量LPS处理6 h后被剖杀,留取孕鼠血清、羊水和胎盘,并检测母血和羊水中一氧化氮(NO)水平,测定胎盘组织还原性谷胱甘肽(GSH)和丙二醛(MDA)含量。结果在高剂量LPS处理前24 h给予的低剂量LPS显著降低高剂量LPS诱导的宫内胎鼠死亡、减少孕鼠血清和羊水中TNF-α含量和降低小鼠胎盘MDA含量。与单纯LPS组比较,LPS(4 h)+LPS组宫内胎鼠死亡率进一步升高、孕鼠血清和羊水中TNF-α与NO含量明显增加、小鼠胎盘MDA含量和GSH损耗也明显提高。结论低剂量LPS预处理对高剂量LPS引起发育毒性的影响取决于两次LPS处理的时距。在高剂量LPS处理孕鼠前24 h给予的低剂量LPS可保护高剂量LPS引起IUFD和早产,主要通过抑制TNF-α产生和对抗机体氧化应激;而在高剂量LPS处理前4 h给予的低剂量LPS却加重高剂量LPS引起的发育毒性。
Objective To investigate the effects of low-dose Lipopolysaccharide （LPS） pretreatment on LPS-induced intra- uterine fetal death（IUFD） and preterm labor. Methods The present study consisted of two separate experiments. Experiment 1, The. pregnant mice were divided into 4 groups randomly. In LPS group, the pregnant mice received an intraperitoneal （i. p. ） injection of LPS （120 μg/kg） on gestational day 15 （GD15）. The control mice received saline （control group）. In LPS 4 h ＋ LPS group, the pregnant mice were pretreated with low-dose LPS （ 10 μg/kg） 4 h before high-dose LPS （ 120 μg/kg） treatment. In LPS 24 h ＋ LPS group, the pregnant mice were pretreated with low-dose LPS （10 μg/kg）24 h before high-dose LPS （120 μg/kg） administration. All animals were observed closely for evidence of preterm labor and delivery. The remaining pregnant mice were sacrificed on GD18. For each litter, the number of live fetuses, dead fetuses, embryo resorption, and implantation sites were counted. Experiment 2, All pregnant mice were divided into 4 groups randomly by using the same methods described above. 12 pregnant mice each group were sacrificed 1.5 h after high- dose LPS treatment. Maternal serum and amniotic fluid were harvested for measurement of TNF-α and IL-10. Twelve pregnant mice each group were sacrificed 6 h after high-dose LPS administration. Placentas were collected for measurement of glutathione （GSH） and malondialdehyde （MDA）. Maternal serum and amniotic fluid were harvested for measurement of nitrite plus nitrate. Results We found that high-dose LPS-induced IUFD was obviously attenuated when the pregnant mice were pretreated with low-dose LPS 24 h before high- dose LPS treatment. Consistent with its protective effect, when administrated 24 h before high-dose LPS, low-dose LPS pretreatment obviously inhibited the releases of TNF-α in maternal serum and amniotic fluid. Low-dose LPS pretreatment 24 h before high-dose LPS significantly attenuated LPS-induced placental lipid peroxidatlon and GSH depletion. However, when administrated 4 h before high-dose LPS, low-dose LPS pretreatment had no effect on LPS-induced release of TNF-α in maternal serum and amniotic fluid, worsened LPS- induced placental lipid peroxidation and GSH depletlon, and increased nitric oxide production in maternal serum and amniotic fluid. Correspondingly, low-dose LPS pretreatment 4 h before hlgh-dose LPS aggravated LPS-induced IUFD. Conclusion The effects of low- dos,. LPS pretreatment on LPS-induced developmental toxicity depends on the interval between two doses of LPS. When administrated 24 h before high-dose LPS, low-dose LPS pretreatment protects mice against LPS-induced IUFD via counteracting the releases of TNF-α and oxidative stress, whereas low-dose LPS pretreatment 4 h before high-dose LPS aggravated LPS-induced developmental toxicity.
出处
《毒理学杂志》
CAS
CSCD
北大核心
2008年第1期4-7,共4页
Journal of Toxicology
基金
国家自然科学基金(30371667
30572223)
安徽医科大学基金(2006kj13)
关键词
细菌脂多糖
宫内胎儿死亡
发育毒性
细菌脂多糖耐受
Lipopolysaccharide
Intra-uterine fetal death
Developmental toxicity
Hyporesponsiveness
