Mechanism Study Of Acute Hypobaric Hypoxia Combined With Sodium Cyanide Poisoning On Cerebral Blood Flow And Acute Brain Injury In Mice

Objective To explore the effects of acute hypobaric hypoxia combined with sodium cyanide poisoning on cerebral blood flow in mice.To explore the pathological mechanism of cerebral blood flow changes in acute brain injury.This study provides a theoretical and experimental basis for the clinical treatment of acute altitude sickness complicated with sodium cyanide poisoning.Methods The closed anoxic tank and hypobaric oxygen chamber were used to create hypoxia and hypobaric hypoxia(altitude 6km)mouse model,and the hypoxia time was0 min,30 min,60 min,1440 min(hypobaric).Combined sodium cyanide(3.8 mg/kg,ip.)was used to create the corresponding acute poisoning hypoxia mouse model.The behavioral activity,cerebral blood flow and pathological changes of the brain were observed in each group.Oxygen analyzer was used to quantitatively detect air oxygen concentration,laser speckle contrast imaging system was used to detect cerebral blood flow,total superoxidase(T-SOD)and malondialdehyde(MDA)test box were used to detect oxidative stress response of the hippocampus in mice.The protein expressions of Iba1,CD68,Bcl2 and Bax were detected by Weston Blot assay.The morphology and inflammatory immune response of microglia cells were detected by immunofluorescence assay.The karyopyknosis apoptosis of cortical and hippocampal neurons was detected by a one-step TUNEL method.Results The mean survival time of hypoxia mice was 89.3±16.3 min,and that of sodium cyanide combined was 170.7±21.1min(P < 0.001).There was no significant change in the behavior of hyperbaric hypoxic at 5 km altitude,and the activity distance of open field test and the fall off latency of rotating text were significantly reduced(P< 0.01,P < 0.001)at 6 km,and the mortality rate was 52.94% at 8km in mice.Compared with the non-hypoxia group,the cerebral blood flow in 30 min and 60 min hypoxia groups was decreased by 11.48% and 34.60%,respectively(P < 0.001),which was time dependent.Hyperbaric hypoxia decreased by 27.93%,20.89% and 35.49% for 30 min,60min and 1440 min,respectively(P < 0.01,P < 0.05 and P < 0.001).Sodium cyanide aggravates reduces cerebral blood flow that hypoxia cause.Both hypoxia and hypobaric hypoxia can induce oxidative stress injury,immune response and neuronal apoptosis in mouse brain tissue,and sodium cyanide can aggravate the effect of brain injury caused by hypoxia and hypobaric hypoxia.Conclusion The effect of hypobaric hypoxia on reducing cerebral blood flow is stronger than that of hypoxia at normal pressure,and the hypoxia and hypobaric hypoxia induces different degrees of brain damage at different times in mice.The survival time of hypoxia combined with sodium cyanide poisoning is prolonged,and the damage of the central nervous system is aggravated in mice.