Experimental Study On The Effects Of BBG On Rat Hippocampal Injuryed By Acute Carbon Monoxide Poisoning

BackgroundCarbon monoxide is the most common toxic gas causing toxic death.It can cause multiple system damage,including brain damage caused by hypoxia.After acute carbon monoxide poisoning?ACMP?,there will be a series of pathological changes,such as inflammatory reaction,brain edema and so on,which will eventually lead to neuronal apoptosis or necrosis.It is generally believed that inflammation plays an important role in the brain damage induced by CO poisoning.Inhibition of inflammation can promote the recovery of nerve function in patients with CO poisoning.The purinergic ion channel receptor 7?purinergic ligand gated ion channel 7 receptor,P2X₇R?is a adenosine triphosphate gated cation channel.Recently,more and more studies have shown that P2X₇R plays an important role in the pathogenesis of many neuropathic diseases,including Alzheimer's disease,spinal injury,and cerebral ischemia.Brilliant blue G?BBG?is a specific antagonist of P2X₇R.BBG play a neuroprotective effect by inhibiting inflammation in many brain diseases.However,the role of P2X₇R in brain injury caused by ACMP and the effect of BBG on brain damage caused by ACMP remains unclear,and further study is needed.ObjectiveTo explore the role of purinergic ligand gated ion channel 7 receptor?P2X₇R?in brain injury of ACMP,the effects of BBG on hippocampal injury of ACMP in rats were observed.The evidence that BBG can reduce brain injury caused by ACMP will provide an important theoretical basis for clinical intervention in ACMP,and find a new drug target for the treatment of carbon monoxide poisoning.MethodsEighty male Sprague–Dawley?SD?rats were divided into four groups that include Control group;ACMP group;ACMP+BBG group and BBG group.The rat ACMP model were successfully established by intraperitoneal injection of gas CO at 100 ml/Kg.The degree of CO poisoning was determined by the concentration of venous blood HbCO.The expression of P2X₇R mRNA in hippocampal tissue was measured by RT-PCR.A Wet-dry weighing method was used to detect the hippocampus edema.The contents of pro-inflammatory factor?IL-1?,TNF-?,IL-6?in hippocampus tissue were measured by Elisa.Morris water maze test was used to evaluate learning and memory ability.HE staining was carried out to observe the morphological changes in hippocampal CA1 region of rat neural cell structures.ResultsCompared with Control group,the changes in the ACMP group at 6 h after ACMP were as follows:The rat survival rate was reduced to 55%?P<0.01?.The expression of P2X₇R mRNA?P<0.05?and the pro-inflammatory factor IL-1?,TNF-?,IL-6levels?P<0.001;P<0.05;P<0.001?in the hippocampus were significantly increased.The water content increased to 80.72%±0.93%?P<0.05?.The escape latency was significantly increased?P<0.05?,and the exploration time in the target quadrant was significantly reduced?P<0.05?.The results of ACMP+BBB group at 6 h after ACMP compared with ACMP group were as follows:The survival rate was increased to 75%?P<0.05?.The expression of P2X₇R mRNA and the pro-inflammatory factor IL-1?,TNF-?,IL-6 levels in the hippocampus were all significantly decreased?P<0.01?.The water content decreased to 79.56%±0.63%?P<0.05?.The active avoidance response latency was significantly decreased?P<0.05?,and the exploration time in the target quadrant was significantly increased?P<0.05?.After poisoning 3 d:The cell arrangement was disorderly and sparsely,the cell morphology was incomplete,and the nucleus was deeply dyed and retracted in ACMP group.Surprisingly,the morphology of CA1 neuron was obviously improved,the nuclei of pyknosis and deep staining were significantly reduced in ACMP+BBG group.ConclutionBBG,an antagonist of the P2X₇R receptor,can increase the survival rate,reduce the release of hippocampus pro-inflammatory cytokines,inhibit hippocampus edema,improve the learning and memory ability in ACMP,and improve neuron damage in CA1 region induced by ACMP rats.