黄芩素通过激活Nrf2/GPx4轴抑制铁死亡减轻复发性流产

LI Ru-liang; YAN Dan-ping; WU Li; XU Jia; LAI Yu-ling

doi:10.1007/s11655-025-4219-9

Your Location：

Home >

Browse articles >

黄芩素通过激活Nrf2/GPx4轴抑制铁死亡减轻复发性流产

Original Article | Updated：2026-08-04

- 黄芩素通过激活Nrf2/GPx4轴抑制铁死亡减轻复发性流产
- Baicalein Attenuated Recurrent Pregnancy Loss by Inhibiting Ferroptosis via Activation of Nrf2/GPx4 Axis
- 中国结合医学杂志（英文版） 2026年32卷第5期页码：396-406
- Affiliations：
  
  1.Department of Traditional Chinese Medicine, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou ( 510500), China
  2.Department of Traditional Chinese Medicine, Jiangxi Maternal and Child Health Hospital, Nanchang ( 330000), China
  3.Department of Sports Medicine, Guangzhou Sport University, Guangzhou ( 510500), China
- Author bio：
  
  Prof. LAI Yu-ling, E-mail: laiyuling666666@163.com
- Funds：
  
  the Department of Education of Guangdong Province(2023KQNCX035);the Administration of Sports of Guangdong Province(GDSS2022N013)
- DOI：10.1007/s11655-025-4219-9
  中图分类号：
- 录用：2024-12-17，
  
  网络首发：2026-01-15，
  
  纸质出版：2026-05
- Accepted：
Scan QR Code
LI Ru-liang, YAN Dan-ping, WU Li, 等. 黄芩素通过激活Nrf2/GPx4轴抑制铁死亡减轻复发性流产[J]. 中国结合医学杂志（英文版）, 2026,32(5):396-406.

LI Ru-liang, YAN Dan-ping, WU Li, et al. Baicalein Attenuated Recurrent Pregnancy Loss by Inhibiting Ferroptosis via Activation of Nrf2/GPx4 Axis[J]. Chinese Journal of Integrative Medicine, 2026, 32(5): 396-406.
LI Ru-liang, YAN Dan-ping, WU Li, 等. 黄芩素通过激活Nrf2/GPx4轴抑制铁死亡减轻复发性流产[J]. 中国结合医学杂志（英文版）, 2026,32(5):396-406. DOI： 10.1007/s11655-025-4219-9.

LI Ru-liang, YAN Dan-ping, WU Li, et al. Baicalein Attenuated Recurrent Pregnancy Loss by Inhibiting Ferroptosis via Activation of Nrf2/GPx4 Axis[J]. Chinese Journal of Integrative Medicine, 2026, 32(5): 396-406. DOI： 10.1007/s11655-025-4219-9.

摘要

目的：

验证铁死亡在复发性流产（RPL）发病机制中的作用，并探讨黄芩素通过抑制铁死亡减轻 RPL 的作用。

方法：

以 CBA/J（

=60）与 DBA/2（

=50）交配小鼠建立 RPL 模型组，CBA/J 与 BALB/c（

=10）交配小鼠作为对照组。在胚胎发育第 0.5天至第 12.5 天（E0.5–E12.5），对 RPL 模型小鼠（每组 n=10）分别给予黄芩素（10 和 40 mg/kg）、铁死亡抑制剂（ferrostatin-1，5 mg/kg）和铁螯合剂（去铁胺，1 mg/kg）。检测妊娠结局及铁死亡相关指标。通过丙二醛（MDA）评估脂质过氧化水平，通过谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GPx）和超氧化物歧化酶（SOD）活性测定抗氧化系统状态。检测 Fe

浓度分析铁积累情况，并用 Western blotting 检测关键蛋白表达。体外实验中，在 erastin 暴露条件下，向 HTR-8/SVn

eo 细胞补充不同浓度的黄芩素（0.1、0.2 和 0.4 μmol/L）。此外，使用 RSL3 和 si-RNA 分别抑制 HTR-8/SVneo 细胞中谷胱甘肽过氧化物酶 4（GPx4）或核因子红细胞 2 相关因子 2（Nrf2）的表达。检测 HTR-8/SVneo 细胞的细胞活力、细胞毒性、铁死亡相关标志物以及 Nrf2 和 GPX4 蛋白表达，以确定黄芩素抗铁死亡的信号通路。

结果：

黄芩素显著减轻了 RPL 小鼠的流产率（

0.01）和胎盘损伤。此外，黄芩素抑制了小鼠胎盘铁死亡，表现为 MDA、铁含量、酰基辅酶 A 合成酶长链家族表达降低，GSH 和 GPx 水平升高（

0.01），以及抗铁死亡相关蛋白（GPx4、SLC7A11 和 Nrf2）表达增加（

0.01 或

0.05）。在体外，不同浓度的黄芩素可恢复铁死亡诱导剂 erastin 所致 HTR-8/SVneo 细胞的损伤和脂质过氧化，但抑制 GPx4 会减弱黄芩素的保护作用（

0.01）。此外，沉默 Nrf2 显著降低了 GPx4 的表达（

0.01），并消除了黄芩素在 HTR-8/SVneo 细胞中介导的抗铁死亡效应。

Abstract

Objective:

To verify effect of baicalein on recurrent pregnancy loss (RPL) and explore its mechanism via inhibition of ferroptosis.

Methods:

In vivo

CBA/J (

=60) mated DBA/2 (

=50) mice were established as RPL group

while CBA/J mated BALB/c (

=10) mice were regarded as control group. Baicalein (10 and 40 mg/kg)

ferroptosis inhibitor (ferrostatin-1

5 mg/kg) and iron chelator (deferoxamine

1 mg/kg) were administered in the RPL mice model (

=10 per group) from embryonic day 0.5–12.5 (E0.5–E12.5). Pregnancy outcomes and ferroptosis related markers were detected. Lipid peroxidation was assessed by malondialdehyde (MDA) and antioxidant system was determined by glutathione (GSH)

glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity. The Fe

concentration was tested to analyze iron accumulation and Western blotting was performed to detect key protein expressions.

In vitro

different concentrations of baicalein (0.1

0.2

and 0.4 μmol/L) were supplemented under the exposure of erastin in HTR-8/SVneo cells. Moreover

RSL3 and si-RNA were used to suppr

ess the expression of glutathione peroxidase 4 (GPx4) or nuclear factor erythroid 2-related factor 2 (Nrf2)

respectively

in HTR-8/SVneo cells. Cell viability

cytotoxicity

ferroptosis related markers

protein expressions of Nrf2 and GPX4 were detected in HTR-8/SVneo cells to determine the signaling pathway of baicalein against ferroptosis.

Results:

Baicalein significantly attenuated fetal loss (

0.01) and placental damage in RPL mice. Besides

baicalein reduced placental ferroptosis which manifested decreased MDA

iron content

Acyl-CoA synthetase long-chain family protein expression and enhanced GSH and GPx levels (

0.01) as well as increased protein expressions that were resistant to ferroptosis (GPx4

SLC7A11 and Nrf2

0.01 or

0.05).

In vitro

different concentrations of baicalein restored a ferroptosis inducer-erastin induced HTR-8/SVneo cells damage and lipid peroxidation

but GPx4 inhibition diminished the protective effect of baicalein (

0.01). Additionally

Nrf2 silencing notably decreased GPx4 expression (

0.01) and abolished baicalein-mediated anti-ferroptosis effect in HTR-8/SVneo cells.

Conclusion:

Baicalein has a protective effect on RPL via inhibiting ferroptosis through Nrf2/GPx4 signaling axis.

关键词

Keywords

references

浏览量

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

Berberine Inhibits Ferroptosis and Stabilizes Atherosclerotic Plaque through NRF2/SLC7A11/GPX4 Pathway

Baicalein Attenuates Severe Polymicrobial Sepsis via Alleviating Immune Dysfunction of T Lymphocytes and Inflammation

Effect and Mechanisms of Electroacupuncture on Mucosal Healing in Ulcerative Colitis Mice via Non-neuroronal Cholinergic System

Aromatherapy Improves Pain, Sleep and Physiological Parameters in Laparoscopic Cholecystectomy Patients: A Single-Blind, Parallel Group, and Randomized Controlled Trial

Total Flavonoids of Litchi chinensis Sonn. Seed Improves Hepatic Fibrosis by Inhibiting PANoptosis