OBJECTIVE To explore the protective effect of baicalein on ferroptosis after intracerebral hemorrhage in rats based on the nuclear factor E2 related factor(Nrf2)/glutathione peroxidase 4(GPX4) pathway.
METHODS Fifty SD rats were randomly divided into 5 groups: sham operation group, model group, baicalein group, baicalein + RSL3 group and baicalein + ML385 group. Basal ganglia injection 60 μL autologous arterial blood was used to establish intracerebral hemorrhage model. Baicalein(100 mg·kg−1), RSL3(10 mg·kg−1) and ML385(10 mg·kg−1) were injected intraperitoneally for 6 d. The neurological function was evaluated by modified neurological severity score(mNSS), the content of iron was detected by chemical colorimetric method, the content of lipid peroxide(LPO) was detected by ELISA, the content of glutathione(GSH) was detected by enzyme labeling, the expression of GPX4 and Nrf2 mRNA was detected by RT-PCR, the expression of Nrf2 and GPX4 protein was detected by Western blotting, and the changes of mitochondria were observed by electron microscope.
RESULTS Compared with the sham-operated group, the mNSS score, iron, LPO, neuronal mitochondrial damage, GPX4 mRNA and Nrf2 mRNA in the model group increased significantly, while GSH, GPX4 protein and Nrf2 protein decreased. Compared with the model group, GSH, GPX4 mRNA, GPX4 protein, Nrf2 mRNA and Nrf2 protein in baicalein group increased, while mNSS score, iron, LPO and neuronal mitochondrial damage decreased. Compared with the baicalein group, the mNSS score, iron, LPO and neuronal mitochondrial damage in the baicalein+RSL3 group increased, GSH and GPX4 protein decreased, the mNSS score, iron, LPO and neuronal mitochondrial damage in the baicalein+ML385 group increased, GSH, GPX4 mRNA, GPX4 protein and Nrf2 protein decreased.
CONCLUSION Baicalein can reduce ferroptosis after intracerebral hemorrhage, and its mechanism may be related to the activation of Nrf2/GPX4 pathway.
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