奥格列汀和去铁胺联合用药对小鼠急性脑出血的神经保护作用OACSTPCD

Objective To investigate the therapeutic effect of the combination of omarigliptin(MK3102)and deferoxamine(DFO)in adult C57/BL male mice with intracerebral hemorrhage(ICH).Methods Collagenase was stereotactically injected into the striatum of mice to induce ICH.Two hours after ICH,mice were given oral gavage with the drug omarigliptin(7 mg/(kg·d))and intraperitoneal injection of deferoxamine(100 mg/(kg·d))for single drug injection and combination therapy,respectively,for three consecutive days.The ICH control group was treated with physiological saline.Mice were euthanized for 3 days to examine iron deposition,activation of microglia/macrophages,neuronal death,brain injury areas,neurological deficits,and blood-brain barrier permeability.Results After systemic administration of omarigliptin and/or deferoxamine,Perls staining,AIFM2,GPX4 immunohistochemistry staining,Western Blot and other tests were performed.The results showed that the degree of ferroptosis was reduced after treatment for intracerebral hemorrhage.Immunofluorescence staining showed that after drug treatment,the number of activated microglia/macrophages,cell death,and neuronal death were significantly reduced after ICH.Meanwhile,compared with the ICH control group,the neurological deficits and brain injury areas caused by ICH were significantly improved after treatment with omarigliptin and/or deferoxamine.In addition,compared to the single treatment group,combination therapy showed better effects in improving ferroptosis and neuroprotection.Conclusion Combination therapy can significantly improve ferroptosis after ICH,inhibit the activation of microglia/macrophages,reduce the permeability of the blood-brain barrier,reduce the number of neuronal deaths,alleviate brain injury areas,and improve neurological deficits after ICH.