烟酰胺通过降低氧化应激水平缓解不对称二甲基精氨酸诱导的胎鼠宫内生长受限

doi:10.3969/j.issn.1006-7795.2025.06.017

首都医科大学学报

烟酰胺通过降低氧化应激水平缓解不对称二甲基精氨酸诱导的胎鼠宫内生长受限

戴岩，桑秀波，白文佩^*#，张瑾^*#

首都医科大学附属北京世纪坛医院妇产科，北京 100038

收稿日期:2025-02-28 修回日期:2025-09-08 出版日期:2025-12-19 发布日期:2025-12-19
通讯作者: 白文佩,张瑾 E-mail:baiwp@bjsjth.cn, zhangjin2494@bjsjth.cn
基金资助:
北京市属医院科研培育计划项目(PX2025027)，首都医科大学附属北京世纪坛医院科研基金项目(2021-q03)。

Nicotinamide ameliorate ADMA-induced fetal growth restriction in mice via reducing oxidative stress levels

Dai Yan, Sang Xiubo, Bai Wenpei^*#, Zhang Jin^*#

Department of Gynecology and Obstetrics, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China

Received:2025-02-28 Revised:2025-09-08 Online:2025-12-19 Published:2025-12-19
Supported by:
This study was supported by Beijing Municipal Administration of Hospitals Incubating Program(PX2025027), Research Fund of Beijing Shijitan Hospital, Capital Medical University(2021-q03).

摘要/Abstract

摘要： 目的通过小鼠体内实验阐明不对称二甲基精氨酸(asymmetric dimethylarginine, ADMA)通过诱导氧化应激导致胎儿生长受限(fetal growth restriction, FGR)的作用，并探讨烟酰胺(nicotinamide, NAM)对FGR的保护作用及机制。方法采用ADMA颈背部注射建立FGR小鼠模型，实验分为对照组、ADMA组、NAM组、ADMA+NAM组。通过检测胎鼠体重评估FGR小鼠模型是否构建成功。将胎盘组织进行苏木精－伊红(hematoxylin-eosin, HE)染色并观察绒毛及间质形态学变化。通过酶联免疫吸附试验(enzyme-linked immunosorbent assay, ELISA)检测胎盘及血清中ADMA水平；采用生化检验法检测胎盘中丙二醛(malondialdehyde, MDA)、谷胱甘肽(glutathione, GSH)、氧化型谷胱甘肽(glutathione disulfide, GSSG)及总谷胱甘肽(total glutathione, T-GSH)浓度；通过荧光定量分析胎盘中活性氧(reactive oxygen species, ROS)水平；通过蛋白质免疫印迹(Western blotting, WB)实验检测胎盘中超氧化物歧化酶1(superoxide dismutase 1, SOD1)及B细胞淋巴瘤/白血病－2抗凋亡蛋白（B-cell lymphoma-2，Bcl-2）表达水平。结果与对照组、NAM组、ADMA+NAM组相比，ADMA组FGR发生率显著升高，且存在胎盘发育不良，差异有统计学意义。与对照组相比，ADMA组小鼠胎盘中MDA、ROS表达水平上升，GSH/GSSG表达水平下降，差异有统计学意义；通过WB证实ADMA组SOD1、Bcl-2蛋白表达水平下降，差异有统计学意义。NAM可通过降低氧化应激水平显著改善ADMA诱导的胎盘发育障碍及FGR。结论孕早期应用适当剂量的NAM可通过改善氧化损伤缓解ADMA诱导的胎盘功能障碍和FGR的发生。

关键词: 胎儿生长受限, 不对称二甲基精氨酸, 氧化应激, 烟酰胺, 小鼠模型, 凋亡

Abstract: Objective To elucidate the role of asymmetric dimethylarginine (ADMA) on fetal growth restriction (FGR) induced by oxidative stress in vivo experiments in mice, and to explore the protective effect of nicotinamide (NAM) on FGR and its mechanism. Methods The FGR mouse model was established by injecting ADMA on the nape of the neck, and the experiment was divided into the control group, ADMA group, NAM group, and ADMA + NAM group. The successful construction of the FGR mouse model was evaluated by detecting the weight of fetal mice. The placental tissues were stained with hematoxylin-eosin (HE) and the morphological changes of villi and interstitium were observed. The levels of ADMA in placenta and serum were detected by enzyme-linked immunosorbent assay (ELISA). Biochemical tests were used to detect the levels of malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), and total glutathione (T-GSH) in placenta. Additionally, the level of reactive oxygen species (ROS) in placenta was quantitatively analyzed by fluorescence. The expression levels of superoxide dismutase 1 (SOD1) and anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) in placenta were detected by Western blotting (WB) experiments. Results In comparison to the control, NAM, and ADMA+NAM group, the incidence of FGR in the ADMA group was significantly increased, and placental dysplasia was observed. Moreover, the ADMA group displayed significantly higher levels of MDA and ROS, and lower levels of GSH/GSSG of the placenta in mice, in contrast to the control group. Additionally, the expression levels of SOD1 and Bcl-2 proteins in the ADMA group decreased, when compared to the control group. NAM can significantly improve placental developmental disorders and FGR induced by ADMA through reducing oxidative stress levels. Conclusion The application of an appropriate dose of NAM in early pregnancy could alleviate ADMA-induced placental dysfunction and FGR by improving oxidative damage.

Key words: fetal growth restriction, asymmetric dimethylarginine, oxidative stress, nicotinamide, mouse model, apoptosis

中图分类号:

R714.2

戴岩, 桑秀波, 白文佩, 张瑾. 烟酰胺通过降低氧化应激水平缓解不对称二甲基精氨酸诱导的胎鼠宫内生长受限[J]. 首都医科大学学报, doi: 10.3969/j.issn.1006-7795.2025.06.017.

Dai Yan, Sang Xiubo, Bai Wenpei, Zhang Jin. Nicotinamide ameliorate ADMA-induced fetal growth restriction in mice via reducing oxidative stress levels[J]. Journal of Capital Medical University, doi: 10.3969/j.issn.1006-7795.2025.06.017.

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烟酰胺通过降低氧化应激水平缓解不对称二甲基精氨酸诱导的胎鼠宫内生长受限

Nicotinamide ameliorate ADMA-induced fetal growth restriction in mice via reducing oxidative stress levels

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