Study on the effect and mechanism of Wenyang huayu formula in improving cerebral ischemia-reperfusion injury in rats
- VernacularTitle:温阳化瘀方改善大鼠脑缺血再灌注损伤的作用及机制研究
- Author:
Tingting XIE
1
;
Zhiying GONG
1
;
Wei MA
1
;
Xueni MO
1
Author Information
1. Institute of Traditional Chinese and Zhuang-Yao Ethnic Medicine,Guangxi University of Chinese Medicine,Nanning 530023,China
- Publication Type:Journal Article
- Keywords:
Wenyang huayu formula;
cerebral ischemia-reperfusion injury;
Nrf2/GPX4 signaling pathway;
mitochondrion;
ferroptosis;
neuron
- From:
China Pharmacy
2026;37(11):1422-1427
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the improving effect and mechanism of Wenyang huayu formula on cerebral ischemia-reperfusion injury in rats based on nuclear factor-erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway and mitochondrial ferroptosis pathway. METHODS SD rats were randomly divided into sham operation group, model group,Nimodipine tablet group (10.8 mg/kg ), and Wenyang huayu formula group (28 g/kg), with 24 rats in each group. Except for the sham operation group, rats in other groups were all subjected to middle cerebral artery occlusion model by Longa thread occlusion method. After successful modeling, rats in each administration group were intragastrically gavaged with corresponding liquid for 7 days or 14 days, while rats in sham operation group and model group were given equal volume of normal saline once a day. At 7 and 14 days after administration, neurological deficit scores of rats were calculated; the ultrastructure of neuronal mitochondria in ischemic brain tissue of rats was observed;the contents of malondialdehyde (MDA), glutathione (GSH) and Fe 2+ , as well as the protein and mRNA expression levels of Nrf2, solute carrier family 7 member 11 (SLC7A11) and GPX4 in ischemic brain tissue of rats were detected. RESULTS At 7 and 14 days after administration, compared with the sham operation group, the neuronal mitochondria in ischemic brain tissue of rats in the model group showed typical changes of ferroptosis, and the injury continued to worsen over time; the neurological deficit scores, the contents of MDA and Fe 2+ were significantly increased ( P <0.05),while the content of GSH and the protein and mRNA expression levels of Nrf2, SLC7A11 and GPX4 were significantly decreased ( P <0.05). Compared with the model group, the morphology of neuronal mitochondria in ischemic brain tissue of rats in Nimodipine tablet group and Wenyang huayu formula group was gradually improved over time, and the above quantitative indicators were significantly reversed ( P <0.05);moreover, the improvement effect of most indicators in Wenyang huayu formula group was significantly better than that in Nimodipine tablet group ( P <0.05). CONCLUSIONS Wenyang huayu formula can improve cerebral ischemia-reperfusion injury in rats, and its mechanism may be related to activating Nrf2/GPX4 signaling pathway and inhibiting mitochondrial ferroptosis.