养血安胎方对复发性自然流产小鼠胎盘铁死亡的调控作用研究

doi:10.19803/j.1672-8629.20240692

摘要/Abstract

摘要： 目的探讨养血安胎方对复发性自然流产（RSA）小鼠胎盘铁死亡的调控作用。方法细胞实验分3组,对照组加入10%空白血清,Erastin组加入25μmol·L^-1Erastin诱导铁死亡,Erastin+养血安胎组加入25μmol·L^-1Erastin并使用10%养血安胎含药血清干预,Western Blot法检测JEG-3细胞中铁蛋白重链1（FTH1）和膜铁转运蛋白l（FPN1）的蛋白表达;动物实验分4组,每组4只动物,正常妊娠组和RSA组灌胃蒸馏水,养血安胎组和RSA+养血安胎组灌胃给予28.08 g·kg^-1养血安胎方溶液,测定胎盘中超氧化物歧化酶（SOD）活力,还原型谷胱甘肽（GSH）、丙二醛（MDA）及二价铁离子（Fe²⁺）的含量,Western Blot法检测胎盘中谷胱甘肽过氧化物酶4（GPX4）、溶质载体家族7成员11（SLC7A11）、血红素氧合酶1（HO-1）、FTH1、FPN1、转铁受体蛋白1（TfR1）和二价金属离子转运体（DMT1）的蛋白表达。结果与对照组比较,Erastin组JEG-3细胞中FTH1和FPN1的蛋白表达均显著降低,与Erastin组比较,Erastin+养血安胎组JEG-3细胞中FTH1和FPN1的蛋白表达均显著增加;与正常妊娠组比较,RSA组中SOD的活力及GSH 的含量显著降低,MDA及Fe²⁺的含量均显著增加;GPX4、SLC7A11、HO-1、FTH1及FPN1的蛋白表达显著降低,TfR1及DMT1的蛋白表达显著增加。与RSA组比较,RSA+养血安胎组中SOD的活力及GSH的含量显著增加,MDA及Fe²⁺的含量显著降低;GPX4、SLC7A11、HO-1、FTH1及FPN1的蛋白表达显著增加,TfR1及DMT1的蛋白表达显著降低。结论养血安胎方能够减轻氧化应激,减少Fe²⁺的摄入,增加Fe²⁺的存储与转出,从而减少Fe²⁺的集聚,抑制铁死亡的发生。

关键词: 养血安胎方, 中药复方, 复发性自然流产, 铁死亡, 氧化应激, 小鼠, 大鼠, 胎盘

Abstract: Objective To investigate the regulatory effect of Yangxue Antai prescription on placental ferroptosis in recurrent spontaneous abortion (RSA) mice. Methods Cell experiment was divided into three groups. In Control group, 10% blank serum was added. In Erastin group, 25 μmol·L^-1 Erastin was added to induce ferroptosis. In Erastin+Yangxue Antai group, 25 μmol·L^-1 Erastin was added and intervened with 10% Yangxue Antai serum. The protein expressions of ferritin heavy chain 1 (FTH1) and ferroportin 1 (FPN1) in JEG-3 cells were measured by Western blot. Animal experiment was divided into four groups with four animals in each group. Normal pregnancy group and RSA group were intragastrically administered with distilled water. Yangxue Antai group and RSA+Yangxue Antai group were intragastrically administered with 28.08 g·kg^-1 of Yangxue Antai prescription. The activity of superoxide dismutase (SOD), the contents of reduced glutathione (GSH), malondialdehyde (MDA) and ferrous ion (Fe²⁺) in mouse placenta were measured. The protein expression of glutathione peroxidase 4 (GPX4), solute carrier family 7, member 11 (SLC7A11), heme oxygenase 1 (HO-1), FTH1, FPN1, transferrin receptor protein 1 (TfR1) and divalent metal transporter 1 (DMT1) in mouse placenta were measured by Western blot. Results Compared with the control group, the protein expressions of FTH1 and FPN1 in JEG-3 cells in the Erastin group were significantly decreased. Compared with the Erastin group, the protein expressions of FTH1 and FPN1 in JEG-3 cells in the Erastin+Yangxue Antai group were significantly increased. Compared with the normal pregnancy group, the SOD activity, GSH and Fe²⁺ contents in placentas in the RSA group were significantly decreased, but the MDA content was significantly increased. The protein expressions of GPX4, SLC7A11, HO-1, FTH1 and FPN1 were significantly decreased in placentas, while those of TfR1 and DMT1 were significantly increased. Compared with the RSA group, the SOD activity, GSH and Fe²⁺ contents in placentas in the RSA+Yangxue Antai group were significantly increased, while that of MDA was significantly decreased. The protein expressions of GPX4, SLC7A11, HO-1, FTH1 and FPN1 were significantly increased in placentas while those of TfR1 and DMT1 were significantly decreased. Conclusion Yangxue Antai prescription can alleviate oxidative stress, reduce the intake of Fe²⁺, increase the storage and transfer of Fe²⁺, thus inhibiting the accumulation of Fe²⁺ and inhibiting the occurrence of ferroptosis.

Key words: Yangxue Antai Prescription, TCM Formula, Recurrent Spontaneous Abortion, Ferroptosis, Oxidative Stress, Mice, Rats, Placenta

中图分类号:

R977
R984

胡海鹏, 姚伟洁, 冯欣. 养血安胎方对复发性自然流产小鼠胎盘铁死亡的调控作用研究[J]. 中国药物警戒, 2025, 22(6): 621-626.

HU Haipeng, YAO Weijie, FENG Xin. Effects of Yangxue Antai Prescription on Placental Ferroptosis in Recurrent Spontaneous Abortion Mice[J]. Chinese Journal of Pharmacovigilance, 2025, 22(6): 621-626.

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