解放军医学杂志2023，Vol.48Issue(12)：1370-1377,8.DOI:10.11855/j.issn.0577-7402.0333.2023.0828
五味子醇甲对小鼠神经管畸形的预防作用及其机制研究
Study on the preventive effect of schisandrin on neural tube defects in mice and its mechanism
摘要
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.关键词
神经管畸形/五味子醇甲/PI3K/Akt信号通路/预防Key words
neural tube defects/schisandrin/PI3K/Akt signaling pathway/prevention分类
医药卫生引用本文复制引用
茹意,谢良骐,王新亮,肖保国,金小明,马存根,柴智,樊慧杰..五味子醇甲对小鼠神经管畸形的预防作用及其机制研究[J].解放军医学杂志,2023,48(12):1370-1377,8.基金项目
This work was supported by the National Natural Science Foundation of China (81703978),the Natural Science Foundation of Shanxi Province (20210302124293),and the Science and Technology Innovation Ability Cultivation Project of Shanxi University of Chinese Medicine (2020PY-JC-03,2022PY-TH-16) 国家自然科学基金(81703978) （81703978）
山西省自然科学基金(20210302124293) （20210302124293）
山西中医药大学科技创新能力培育项目(2020PY-JC-03,2022PY-TH-16) （2020PY-JC-03,2022PY-TH-16）
