Effect Of Edaravone On Serum TNF-α,IL-6 Concentration And Expression Of NF-κB In A SD Rat Model Of Brain Death

Objective To investigate the establishment and the maintenance of brain-dead model with SD rat.To evaluate the effects of edaravone on the change of hepatic function,morphology and serum TNF-αand IL-6 concentration and NF-κB protein expression of liver of SD rat brain-death state.Materials and Methods Twenty-four 3-4 month healthy SD rats of either sex were randomly assigned to four study groups(n=6):sham(group C);brain death(group B);brain death with edaravone 1(3mg/kg iv before brain death induced,groupI₁)and brain death with edaravone 2(3mg/kg iv at brain death confirmed immediately,groupI₂).groupB,groupI₁,groupI₂ established brain death model and mechanically ventilated for 6 hours after brain death,group C mechanically ventilated for 6 hours after sham operation.Rats were at time before brain death induced(T₁),brain death confirmed(T₂,groupC at 1 hour after sham operation)and 6 hours after brain death(T₃),serum TNF-αand IL-6 concentration were determined. right lobe of liver was removed for morphologic examination by HE staining and determination of NF-κB protein expression by immnohistochemistry.Result The serum ALT and AST concentration were significantly higher in group B,group I₁ and group I₂ than in group C at T₃(P＜0.05). edaravone treatment significantly attenuated the increase in serum ALT and AST concentration in group I₁ and group I₂(P＜0.05).The serum TNF-αand IL-6 concentration were significantly increased in group B,group I₁ and group I₂(P＜0.05)and the concentration were lower in group I₁ and group I₂ than in group B(P＜0.05).The expression of NF-κB protein of group B was significantly increased,the expression of group C was weak and scattered.Expression of NF-κB protein for group B,group I₁ and group I₂ was significantly increased than that for group C(P＜0.05),the expression of group I₁ and group I₂ was lower than that of group B(P＜0.05).Morphological changes of hepatic tissues:in group C,hepatic tissues appearances were normal.In group B,obvious edema of partial cells. Liver injury was significantly attenuated in group I₁ and group I₂.Conclusion 1.To establish brain-dead model by increasing intracranial pressure in a modified,slow and intermittent way with AAI monitoring in SD rat can effectively mimic the clinical brain death.With effective respiration and circulation support,the brain-dead state could be maintained.2.Brain death may evoke hepatic morphological injury of SD rats.3.Serum TNF-αand IL-6 concentration and t NF-κB protein expression in the liver tissues can be enhanced by the brain death.Serum TNF-αand IL-6 concentration and t NF-κB protein expression in the liver tissues were significantly attenuated in group I₁ and group I₂ by edaravone treatment.4.edaravone has protection which can against the liver injury caused by brain death.