Study on the preventive effect of schisandrin on neural tube defects in mice and its mechanism / 解放军医学杂志

ABSTRACT

Objective To investigate the preventive effect of schisandrin(SCH)on fetal neural tube defects(NTDs)of mice and its mechanism.Methods C57BL/6 mice were mated with female and male at a ratio of 2:1.Pregnant female mice with vaginal plug after mating were randomly divided into control group,model group,SCH group,and folic acid group,with 9 mice in each group.The NTDs fetal mice model was induced by intraperitoneal injection of all-trans retinoic acid(atRA)(7.5 mg/kg)on embryonic day 7.5(E 7.5 d).During E 0.5 d-E 11.5 d,pregnant rats in folic acid group were given folic acid[61.0 μg/(kg·d)]by gavage once a day,and pregnant rats in SCH group were given SCH[8.0 mg/(kg·d)]by gavage once a day.Fetal mice were removed by cesarean section on E 11.5 d.PC12 cells were divided into control group,model group and SCH group.PC12 cells were treated with atRA(20 μmol/L)for 12 hours to establish cell damage model in model group,and treated with SCH(2.5 μmol/L)for 24 hours in SCH group.Fetuses were identified NTDs by stereoscopic microscopy.HE staining was used to observe the closure of the neural tube.The expression levels of p-PI3K,Akt and p-Akt molecules in PI3K/Akt signaling pathway were detected by Western Blotting.Results Compared with control group,the incidence of NTDs was significantly increased in mice of model group(P<0.01);compared with model group,the incidence of NTDs was decreased in folic acid group and SCH group(P<0.01);compared with folic acid group,SCH group had a lower incidence of NTDs(P<0.01).Western Blotting results showed that compared with control group,the expression of p-PI3K and p-Akt protein in fetal tissues of model group was significantly decreased(P<0.01,P<0.05);compared with model group,there was no significant difference in expression of p-PI3K and p-Akt in fetal tissues of folic acid group(P>0.05),while the expression of p-PI3K and p-Akt protein in SCH group was significantly higher(P<0.05).Compared with control group,PC12 cells in model group showed lower expression levels of p-PI3K and p-Akt(P<0.05);compared with model group,PC12 cells in SCH group showed higher expression levels of p-PI3K and p-Akt(P<0.05).Conclusions SCH can reduce the incidence of atRA-induced NTDs in fetal mice,and its preventive effect is better than folic acid,which may be related to the activation of the PI3K/Akt signaling pathway.