Mechanism of dihydromyricetin attenuates on brain damage in rats with traumatic brain injury and sea-water immersion hypothermia
Objective This study aims to explore the mechanism of dihydromyricetin attenuates on brain damage in rats with traumatic brain injury and seawater immersion hypothermia.Methods A total of 36 male SD rats were randomly divided into three groups:Sham group(n=12),TBI+SIH group(n=12),and DMY treatment group(n=12).The controlled cortical impact(CCI)cranio-cerebral injury method and constant temperature water bath soak-ing method were used to establish the TBI+SIH rat model.DMY was intraperitoneally injected at a dose of 300 mg/kg every 24 hours.The modified neurological deficit score(mNSS)and open field test were performed to evaluate the neurological function of rats at 72 h after the model was successfully prepared.The rats were killed after the behavioral test,and the water content and Ev-ans blue(EB)content of brain tissue were measured.Hematoxylin-eosin(HE)staining was used to observe the morphology of brain tissue,Prussian blue staining was used to observe the iron deposition in brain tissue,and transmission electron microscopy was used to observe the ultrastructural changes of neurons.Kits were used to detect the iron content,malondialdehyde(MDA)content,glutathione(GSH)content and the levels of inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 in the brain tissue around the injury.Western blotting was applied to detect the expression of glutathione peroxidase 4(GPX4).Results The pathological examination showed scattered bleeding and deformation of tissue and cell structure in TBI+SIH group.In the DMY treatment group,cerebral edema was more obvious and cerebral hemorrhage was more serious.Under the transmission electron micro-scope,mitochondria in TBI+SIH group were shrunk,mitochondrial membrane was thickened and the cristae were broken.In the DMY treatment group,the nuclear chromatin was partially edged and mitochondrial damage was reduced.Compared with the TBI+SIH group,the neurological function score of rats in the DMY treatment group was reduced,and the MDA,iron content,TNF-α,IL-1β,and IL-6 content in brain tissue were significantly reduced(all P＜0.05),while the GSH content and GPX4 expression were significantly in-creased(all P＜0.05).Conclusion DMY can alleviate brain damage in TBI+SIH rats,and its mechanism may be related to the inhi-bition of the inflammatory response and GPX4-mediated ferroptosis.
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