Molecular Mechanism Of Brain Damage Induced By Carbon Monoxide Poisoning And Feasibility Analysis Of Xingzhi Yinao Particles

Objective:To investigate the effect of Xing-Zhi-Yi-Nao（XZYN）particles on the expressions of Nogo and OMgp proteins in brain of rats after acute carbon monoxide（CO）poisoning.Methods:A total of 120 Sprague-Dawley rats were randomly divided into normal group,CO poisoning group and XZYN particles treatment group（40 rats in each group）.The rat in CO poisoning group and treatment group of acute CO poisoning were established by using an animal chamber,and then received hyperbaric oxygen therapy.Meanwhile,rats in treatment group were further given additional XZYN particles by gavage.At 1 day,1 week,1 month and 2 months after CO poisoning,the neurobehavioral score of rats was evaluated by a Morris water maze test and a shuttle box test,and the expressions of neurite outgrowth inhibitor（Nogo）and oligodendrocyte-myelin glycoprotein（OMgp）were investigated in rat brain tissue by immuneohistochemistry staining and western blot assay,respectively.Results:Compared with those in normal control group[（11.6±8.4）s、（41.8±4.4）%、（16.1±2.3）sand（1.2±0.2）s],the escape latency in CO group was significantly prolonged[（14.1±6.1）s],and the T₁/T total was obviously decreased[（23.6±2.4）%],the escape time[（26.3±3.8）s],the active escape latency[（2.3±0.3）s]were notably extended at 1d（P<0.05）.The cognitive dysfunction caused by CO poisoning was more obvious in the later stage of poisoning（from 1 week to 2 months,P<0.05）.Compared with those in CO group,the escape latency was significantly shortened[from（3.5±0.6）s to（3.1±0.5）s],the T₁/T total was gradually increased[from（29.7±3.2）%to（36.7±3.2）%],the escape time[from（39.7±5.4）s to（18.1±2.0）s]and the active escape latency were obviously decreased[from（4.3±0.4）s to（2.1±0.2）s]in the later stage（>1 week）in Xing-Zhi-Yi-Nao treatment group（P<0.05）.The expression of Nogo and OMgp proteins in brain tissue in CO poisoning group were gradually increased as time went by.The increased expressions of Nogo and OMgp proteins were still observed at 1 month after CO poisoning.By contrast,XZYN particles could significantly improve cognitive function,reduce the expression of Nogo protein,and there was statistical difference compared with the poisoning group（P<0.05）.However,the level of OMgp protein in XZYN treatment group was slightly lower than that in CO poisoning group,but there was no difference between the two groups（P>0.05）.Conclusions:The expressions of Nogo and OMgp proteins may be associated with brain injury and demyelination in rats induced by CO poisoning.XZYN particles can down-regulate the expressions of Nogo,and pave a way for the treatment of acute brain damage and delayed encephalopathy after CO poisoning.Objective:To investigated the therapeutic effects of Xing-Zhi-Yi-Nao（XZYN）particles combined with hyperbaric oxygen therapy on cognitive impairment and motor dysfunction in patients with delayed encephalopathy after acute carbon monoxide poisoning（DEACMP）.Methods: Sixty-seven patients with DEACMP were admitted to the Affiliated Yantai Yuhuangding Hospital of Qingdao University from January 2011 to December 2015.According to the patient’s and family’s willingness,they were divided into: conventional treatment control group（n=19 cases）,hyperbaric oxygen treatment group（HBO group,n=24 cases）,Xing-Zhi-Yi-Nao particles treatment group（XZYN group,n=24 cases）.The conventional treatment group was treated with oxygen + cytidine diphosphate cholin + vitamin B;the HBO group was given hyperbaric oxygen treatment once a day on the basis of conventional treatment;the XZYN group was given conventional treatment + hyperbaric oxygen +Xing-Zhi-Yi-Nao free frying particles treatment for 2 months.Before and after treatment for 1 to 2 months,the cognitive function and motor function of the patients were evaluated by the use of activity of daily living（ADL）scale,Montreal cognitive assessment（Mo CA）scale,and mini-mental state examination（MMSE）scale;the severity of cerebral white matter injury was assessed by age related white matter changes（ARWMC）scale;and the electromyographic evoked potential was used to detect the amplitude and latency of P300 to assess the severity of cognition impairment and prognosis.Results: With the prolongation of therapeutic time,after treatment,the neurological function scores of ADL,Mo CA,MMSE and amplitude of P300 were increased,while ARWMC was decreased and the latency of P300 was shortened gradually in the three groups,and the changes of above indexes after treatment for 2 months in XZYN group [ADL score: 70.2±8.3,Mo CA score: 26.1±3.1,MMSE score: 25.9±4.1,ARWMC score: 7.0±2.1,latency of P300（ms）: 332.9±20.4,amplitude of P300 （μV）: 6.5±1.6] were more significant than those in either HBO group [ADL score: 60.5±8.1,Mo CA score: 22.2±2.7,MMSE score: 22.4±3.5,ARWMC score: 8.7±2.2,latency of P300（ms）: 352.5±23.6,amplitude of P300（μV）: 5.6±1.3] or control group [ADL score: 23.0±6.1,Mo CA score: 18.2±3.6,MMSE score: 18.1±4.5,ARWMC score: 15.2±3.3,latency of P300（ms）: 381.7±30.3,amplitude of P300（μV）: 4.1±1.5].（P< 0.05）.Conclusions: The hyperbaric oxygen therapy combined with XZYN particles for treatment of patients with DEACMP can significantly improve their cognitive and motor functions and ameliorate the severity of cerebral white matter injury.