N-乙酰半胱氨酸在脂多糖诱发的胚胎损害中的双向作用

A dual effect of N-acetylcysteine on lipopolysaccharide-induced fetal damage in mice

目的研究N-乙酰半胱氨酸(NAC)预处理和后处理对细菌脂多糖(LPS)引起宫内胎鼠死亡(IUFD)和生长发育迟缓(IUGR)的影响。方法实验1:LPS组小鼠于妊娠d15～17经腹腔注射LPS(75μg·kg-1),LPS+NAC组在LPS处理前和(或)处理后经腹腔注射给予NAC。所有孕鼠于妊娠d18处死。实验2:LPS组小鼠于妊娠d15注射LPS,LPS+NAC组在LPS处理前和(或)处理后经腹腔注射给予NAC。LPS处理后1.5h或6h处死孕鼠。结果LPS+NAC预处理组平均每窝死胎数明显低于LPS组;LPS+NAC后处理组平均每窝死胎数与LPS组比较无差异,LPS+NAC后处理组流产率高于LPS组;LPS+NAC预处理和后处理均抑制LPS引起IUGR。NAC预处理抑制LPS引起母肝、胎肝和胎盘组织脂质过氧化,LPS+NAC后处理抑制LPS引起母肝组织脂质过氧化,但对LPS引起的胎肝和胎盘组织脂质过氧化无抑制作用。进一步研究发现,母鼠妊娠期给予LPS后,血清TNF-α水平上升,NAC预处理抑制LPS引起血清和羊水TNF-α水平上升,而NAC后处理对LPS引起血清TNF-α水平上升无影响。结论NAC预处理预防LPS引起IUFD和IUGR;NAC后处理对LPS引起IUFD和IUGR无影响,反而加重早产。

Aim To investigate the effect of N-acetylcysteine （NAC） pretreatment/posttreatment on lipopolysaccharide （LPS）-induced intra-uterine fetal death （IUFD） and intra-uterine growth retardation （IUGR） in mice.Methods In the first experiment,all pregnant mice except controls received an intraperitoneal （75 μg·kg-1） injection of LPS on gd 15~17.In LPS＋NAC groups,the pregnant mice were treated with NAC before and/or after LPS. The saline-and NAC-treated pregnant mice served as controls. The dams were sacrificed on gd 18. In the second experiment,all pregnant mice except controls received an intraperitoneal （75 μg·kg-1） injection of LPS on gd 15. In LPS＋NAC groups,the pregnant mice were treated with NAC before and/or after LPS. The saline-and NAC-treated pregnant mice served as controls. The dams were sacrificed at 1.5 h or 6 h after LPS.Results pretreatment with NAC significantly alleviated LPS-induced fetal mortality and reversed LPS-induced growth development retardation.Correspondingly,pretreatment with NAC significantly attenuated LPS-induced elevation in TNF-α concentration in maternal serum and amniotic fluid and lipid peroxidation in maternal and fetal livers. By contrast to pretreatment,posttreatment with NAC had no effect on LPS-induced TNF-α production and lipid peroxidation,and did not protect against LPS-induced IUFD and IUGR and in fact aggravated LPS-induced preterm labor.Conclusion Pretreatment with NAC attenuates LPS-induced IUFD and IUGR,whereas posttreatment with NAC aggravates LPS-induced preterm labor.