ABSTRACT
Objective To explore the effect and mechanism of necroptosis related proteins in middle cerebral artery occlusion (MCAO) induced brain ischemia/reperfusion injury in mice.Methods C57BL/6 mice were used to establish the brain ischemia/reperfusion injury model induced by MCAO.MCAO mice were treated with z-VAD.fmk (zVAD,1.1 g/kg),GSK'872 (0.7 g/kg) and combined intervention of zVAD and GSK'872,and neurological defect was evaluated by mNSS while brain infarct volume was measured by TTC staining.Western blot and immunofluorescence assay were used to detect protein expression and location of RIP1,RIP3 and MLKL,respectively.Results Neurological defect and brain infarction were caused by MCAO.Compared with MCAO group,zVAD,GSK'872 and the combined intervention alleviated neurological defect and reduced brain infarct volume significantly (P＜0.05 or P＜0.01).The protein levels of RIP3 and RIP1 MLKL were increased in mice of MCAO group,while GSK'872 and the combined intervention obviously downregulated the aforementioned protein expression [RIP1 (GSK'872:0.64± 0.02 vs MCAO:1.28±0.02,P＜0.01);RIP3 (GSK'872:1.08±0.02 vs MCAO:1.45±0.02,P＜0.01);MLKL (GSK'872:0.54±0.01 vs MCAO:1.00±0.01,P＜0.01)].However,zVAD only slightly reduced protein expression of MLKL (P＜0.05) but didn't change the protein expression of RIP1 and RIP3 (P＞0.05).Conclusion RIP1,RIP3 and MLKL are involved in the execution of necroptosis and contribute to the pathological progress of brain ischemia/reperfusion injury.
ABSTRACT
Objective To observe the cardiac function in acute brain injury patients(ABI)and the relationship between ABI and plasma neuropeptideY(NPY),and to inspect the mechanism and find the evidences for preventing cardiac impairment caused by ABI. Methods 89 patients with acute brain injury within 24 hours after the injury were divided into severe group(n =47)and mild group(n = 42)according to Glasgow Coma Scale(GCS),and 35 normal healthy adults were selected as control group.In 24 hours and 72 hours after the brain injury,all patients were examined with echocardiography to observe cardiac structure,Doppler blood flow velocity and cardiac function,and in the same time the plasma NPY were determined by radioimmunoassay.Then the results were compared with controls. Results The parameters of cardiac function such as EF、 SV.AV、CO、CI had statistical change in 24 hours and 72hours after the brain injury between severe ABI group and mild ABI group,and it also had statistical change between severe ABI group and control group(all P <0.05),but no statistical change between mild ABI group and control group(all P ＜0.05).The level of plasma NPY in ABI patients was significantly higher than that before injury,there was statistically different change between severe ABI group and mild ABI group,and it also had statistical change between severe ABI group and control group(all P＜0.05).The parameters of cardiac function was negatively correlated with the rise of plasma NPY by pearson correlation analysis(EF:r =- 0.79,P <0.01; SV:r =- 0.71,P <0.01;AV:r=-0.67,P ＜0.01 ;E/A:r =-0.63,all P ＜0.01)and(CO:r =- 0.32,P ＜0.05;CI:r =-0.35,all P ＜0.05). Conclusion The parameters of cardiac function were significantly decreased in the patients with acute brain injury,and it was closely related with the level of plasma NPY.