脑泰方调控细胞铁转运抑制铁死亡保护脑卒中缺血损伤的机制研究

Objective: To explore whether Naotaifang (脑泰方) reduces brain iron deposition by regulating heat shock factor 1 (HSF1)/heat shock proteins B1 (HSPB1) pathway, inhibiting the deposition of reactive oxygen species and the production of lipid peroxidation products, reducing neuronal ferroptosis, and exerting a protective effect on cerebral ischemia injury. Methods: SD rats were randomly divided into sham group, model group, Naotaifang (27 g/kg) group ang deferiprone (125 mg/kg) group, drugs were given for intervention. Cerebral ischemia rats model was prepared by middle cerebral artery occlusion (MCAO) method, and the neurological function was scored 2 h after operation. TTC staining was used to detect cerebral infarct volume;HE staining was used to observe the morphology and damage;Nissl staining was used to observe the number of Nissl bodies;Prussian blue staining was used to observe the level of iron accumulation in neurons;Western blotting and immunohistochemical experiments werre used to detect the protein expression levels of HSF1, HSPB1, transferrin receptor 1 (TFR1) and ferritin heavy polypeptide1 (FTH1);Iron ion detection kits, malondialdehyde detection kits and reactive oxygen detection kits were used to detect brain iron, malondialdehyde and reactive oxygen content. Results: Compared with model group, the cerebral infarction volume of rats in Naotaifang group was decreased, and neurological function score was decreased (P < 0.01);Nissl bodies in cerebral ischemia area was increased, and the degree of cell damage was decreased;Number of iron-containing aggregate granule cells were decreased;Brain iron, malondioxide aldehyde and reactive oxygen content were decreased (P < 0.05, 0.01);HSF1, HSPB1 and FTH1 protein expressions were up-regulated (P < 0.05, 0.01), and TFR1 protein expression was down-regulated (P < 0.05). Conclusion: Naotaifang may up-regulate HSF1/HSPB1 pathway, inhibit the expression of TFR1 to reduce neuronal iron absorption, and increase the expression of FTH1 to increase the iron storage of ferritin, thereby regulating the steady-state balance of iron metabolism, inhibiting excessive ferroptosis of neurons in ischemic stroke caused by active oxygen produced by Fenton reaction and subsequent lipid peroxide. © 2021, Editorial Office of Chinese Traditional and Herbal Drugs. All right reserved.

Mechanism of Naotaifang on ischemic stroke through regulating cellular iron transport and inhibiting ferroptosis