TNF-α在LPS引起小鼠宫内胎儿生长抑制和骨骼发育迟缓中的作用

目的:研究TNF-α在细菌脂多糖(LPS)引起小鼠宫内胎儿死亡(IUFD)、生长抑制(IUGR)和骨骼发育迟缓中的作用。方法:LPS组小鼠在受孕晚期腹腔给予LPS(75μg/kg);LPS+PTX组在LPS处理前30min经腹腔注射给予TNF-α合成抑制剂己酮可可碱(PTX,100mg/kg);对照组给予生理盐水和/或PTX,部分孕鼠给药1d当天处死,部分孕鼠边续给药3d,于孕d18处死,测母肝、胎肝和胎盘的TNF-α等并统计活胎、死胎和吸收胎数,称量活胎体重,测量胎鼠身长和尾长,评价胎鼠骨骼发育情况。结果:①小鼠受孕d15-17给予LPS后,平均每窝死胎数为8.17±1.95,显著高于对照组的0.05±1.09,PTX预处理预防LPS引起的IUFD;LPS处理显著导致胎儿IUGR和骨骼发育迟缓,PTX预处理明显减轻LPS对胎儿的作用。②LPS明显诱导母肝和胎盘组织TNF-αmRNA表达,增加母鼠血清和羊水TNF-α浓度;PTX预处理显著抑制TNF-α产生。结论:孕期给予LPS引起小鼠宫内胎儿死亡、生长抑制和骨骼发育迟缓,TNF-α至少部分参与了LPS引起的宫内胎儿死亡、生长抑制和骨骼发育迟缓。

Role of Tumor Necrosis Factor Alpha on Lipopolysaccharide-induced Intra-uterine Fetal Growth Restriction and Skeletal Development Retardation in Mice

Objective: To investigate the role of tumor necrosis factor alpha(TNF-α) on lipopolysaccharide(LPS)-induced intra-uterine fetal death(IUFD) and intra-uterine growth restriction(IUGR) and skeletal develop-ment retardation in mice.Methods: The timed pregnant mice were injected with LPS(75 μg/kg,i.p.) daily in gestational late stage.The mice were injected by pentoxifylline(PTX)(100 mg/kg) in 30 min before treaded with LPS,in LPS+PTX group,and the control were received physiolegical saline solution and/or PTX.Some mice were killed on the day of injection,and the left were injected the drug continuously and killed on gestational day 18.The number of live fetuses,dead fetuses and resorption sites was counted on gd 18.Live fetuses in each litter were weighed.Crown-rump and tail lengths were examined and skeletal development was evaluated.Results: Maternal LPS exposure significantly increased the number of dead fetuses,lowered fetal weight,reduced crown-rump and tail lengths,and retarded skeletal ossification in caudal vertebrae,anterior and posterior phalanges,and supraoccipi-tal bone.Additional experiment showed that a single dose of LPS(75 μg/kg,i.p.) on gd 15 increased the expression of TNF-α mRNA in maternal liver and placenta and TNF-α concentration in maternal serum and amniotic fluid.Furthermore,pentoxifylline,an inhibitor of TNF-α synthesis,significantly inhibited TNF-α production,reduced fetal mortality,and reversed LPS-induced intra-uterine fetal death,growth restriction and skeletal development retardation.Conclusion: Maternal lipopolysaccharide exposure results in IUFD and IUGR in mice.TNF-α is,at least in part,mediated in LPS-induced IUFD and IUGR.