胆碱对脂多糖诱导的胎儿生长受限大鼠的治疗作用及机制研究

Therapeutic effect and mechanism of choline on fetal growth restriction induced by lipopolysaccharide in rats

目的 过多的促炎细胞因子会导致不良的妊娠结局,包括子痫前期和胎儿生长受限。抗炎可能是一种有效的疗法。本研究的目的是通过LPS治疗是否会出现胎儿生长受限(FGR),并评估胆碱是否可以抑制脂多糖(LPS)诱导的胎儿生长受限大鼠模型中的胎盘炎症并改善妊娠结局。方法 将怀孕的Sprague-Dawley大鼠分为对照组、LPS处理组(LPS)、LPS+胆碱处理组和胆碱处理组(Choline),每组7只。妊娠第14天给予LPS(1μg/kg)建立大鼠模型。胆碱(5.0 g/kg)分别为从GD1到GD20给药,然后在GD20处死大鼠。记录胎儿的丢失,活胎儿的数量和质量以及胎盘的质量。收集胎盘以评估胎盘病理并确定炎性细胞因子和α7nAChR的水平。结果 LPS可加重胎盘病理损伤和增加胎盘炎性细胞因子的水平,降低胎盘α7nAChR水平,并减少活胎的数量并诱发FGR。胆碱治疗增加了胎儿体质量、胎盘质量和活幼崽的数量(P<0.05),减少胎盘炎症反应以及增加了α7nAChR水平。此外,LPS组的胎盘白细胞介素(IL)-6、IL-8和肿瘤坏死因子-α的升高在胆碱给药后得到明显抑制(P<0.01)。结论 胆碱可能通过激活α7nAChR介导的胆碱能抗炎途径来减轻胎盘炎症和改善胎儿结局,这表明胆碱的抗炎作用可能是胎儿生长受限的替代疗法。

Objective Excessive pro-inflammatory cytokines result in adverse pregnancy outcomes including pree-clampsia and fetal growth restriction.Anti-inflammation might be an effective therapy.The research aim to investigate if fetal growth restriction(FGR)occurs with LPS treatment and evaluate whether choline can inhibit placental inflammation in a rat model of lipopolysaccharide(LPS)-induced fetal growth restriction and improve pregnancy outcomes.Methods Pregnant Sprague-Dawley rats were divided into four groups:the control group,the LPS group,the LPS+choline group,and the choline group,with 7 rats in each group.On the 14th day of gestation,LPS(1μg/kg)was given to establish a rat model.Choline(5.0 g/kg)was administered from GD 1 to GD 20,and the rats were killed in GD 20.Loss of fetuses,number of live fetuses,and weights of live fetuses and placentas were recorded.Placentas were collected to evaluate placental pathology and deter-mine inflammatory cytokines andα7 nicotinic acetylcholine receptor(α7nAChR)levels.Results We found that LPS treatment increased levels of placental pathological damage and placental inflammatory cytokines,decreased levels ofα7nAChR,re-duced number of live fetuses and induced FGR.Pretreatment with choline increased fetal weight,placental weight and the number of live pups(P<0.05),decreased placental inflammation and increasedα7nAChR levels.Moreover,increased placental levels of interleukin(IL)-6,IL-8 and tumor necrosis factor-αin the LPS-treated group were obviously inhibited after nicotine administration(P<0.01).Conclusion Choline reduces placental inflammation and improves fetal outcome by activating the cholinergic anti-inflammatory pathway mediated byα7nAChR.It may be an alternative therapeutic strategy for inflammation-induced FGR in pregnancy.