五味子醇甲对小鼠神经管畸形的预防作用及其机制研究

茹意; 谢良骐; 王新亮; 肖保国; 金小明; 马存根; 柴智; 樊慧杰

doi:10.11855/j.issn.0577-7402.0333.2023.0828

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五味子醇甲对小鼠神经管畸形的预防作用及其机制研究

基础研究 | 更新时间：2024-01-04

- 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
- 解放军医学杂志 2023年48卷第12期页码：1370-1377
- 作者机构：
  
  1.山西中医药大学多发性硬化益气活血重点研究室/神经生物学研究中心，山西晋中 030619
  2.复旦大学华山医院神经病学研究所，上海 200025
  3.美国印第安纳大学医学院，印第安纳波利斯 46202
- 作者简介：
  
  茹意，硕士研究生，主要从事神经系统疾病的中西医结合防治研究
  马存根，E-mail：macungen@sxtcm.edu.cn
  樊慧杰，E-mail：fanhuijie@sxtcm.edu.cn
- 基金信息：
  
  国家自然科学基金(81703978);山西省自然科学基金(20210302124293);山西中医药大学科技创新能力培育项目(2020PY-JC-03;2022PY-TH-16)
- DOI：10.11855/j.issn.0577-7402.0333.2023.0828
  中图分类号：
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茹意, 谢良骐, 王新亮, 等. 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.

Ru Yi,Xie Liang-Qi,Wang Xin-Liang,et al.Study on the preventive effect of schisandrin on neural tube defects in mice and its mechanism[J].Medical Journal of Chinese People′s Liberation Army,2023,48(12):1370-1377.
茹意, 谢良骐, 王新亮, 等. 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. DOI： 10.11855/j.issn.0577-7402.0333.2023.0828.

Ru Yi,Xie Liang-Qi,Wang Xin-Liang,et al.Study on the preventive effect of schisandrin on neural tube defects in mice and its mechanism[J].Medical Journal of Chinese People′s Liberation Army,2023,48(12):1370-1377. DOI： 10.11855/j.issn.0577-7402.0333.2023.0828.

摘要

目的,2,探究五味子醇甲(SCH)对小鼠神经管畸形(NTDs)的预防作用及其机制。,方法,2,将C57BL/6小鼠按照雌雄2∶1比例合笼，将交配后有阴栓的雌鼠(孕鼠)随机分为对照组、模型组、SCH组与叶酸组，每组9只。除对照组外，在孕鼠妊娠7.5 d(E 7.5 d)时腹腔注射全反式维甲酸(atRA)(7.5 mg/kg)诱导胎鼠NTDs模型；在E 0.5 d－E 11.5 d，叶酸组孕鼠连续灌胃给予叶酸(61.0 μg/(kg·d)，SCH组孕鼠连续灌胃给予SCH(8.0 mg/(kg·d)，1次/d；在E 11.5 d实行剖宫产手术取出胎鼠。将PC12细胞分为对照组、模型组与SCH组，模型组采用atRA(20 μmol/L)处理12 h建立细胞损伤模型，SCH组再使用SCH(2.5 μmol/L)处理24 h。体视显微镜下鉴定胎鼠NTDs；HE染色观察胎鼠神经管闭合情况；Western blotting检测磷脂酰肌醇-3-激酶/蛋白激酶B (PI3K/Akt)信号通路p-PI3K、Akt、p-Akt蛋白表达水平。,结果,2,与对照组比较，模型组胎鼠NTDs发病率明显升高(,P,<,0.01)；与模型组比较，叶酸组和SCH组胎鼠NTDs发病率降低(,P,<,0.01)；与叶酸组比较，SCH组胎鼠NTDs发病率降低(,P,<,0.01)。Western blotting检测结果显示，与对照组比较，模型组胎鼠组织p-PI3K、p-Akt蛋白表达均明显降低(,P,<,0.01，,P,<,0.05)；与模型组比较，叶酸组胎鼠组织p-PI3K、p-Akt蛋白表达差异无统计学意义(,P,>,0.05)，SCH组p-PI3K、p-Akt蛋白表达明显增高(,P,<,0.05)。与对照组比较，模型组PC12细胞p-PI3K、p-Akt蛋白表达水平降低(,P,<,0.05)；与模型组比较，SCH组PC12细胞p-PI3K、p-Akt蛋白表达水平增高(,P,<,0.05)。,结论,2,SCH可降低atRA导致的胎鼠NTDs发病率，其预防效果优于叶酸，这可能与激活PI3K/Akt信号通路有关。

Abstract

Objective,2,To investigate the preventive effect of schisandrin (SCH) on fetal neural tube defects (NTDs) of mice and its mechanism.,Methods,2,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,2,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,2,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

Keywords

neural tube defectsschisandrinPI3K/Akt signaling pathwayprevention

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