Protective Effect Of Propofol On Neurological Function In Rats After Traumatic Brain Injury

Traumatic brain injury(TBI)is a common neurosurgical disease with high morbidity,high morbidity and high mortality.The neurological damage after TBI will directly affect the patient's quality of life and even increase the family's economic burden.In-depth study of neurological damage and repair mechanisms after TBI,and the search for suitable targets,has become a research hotspot and difficult point of current treatment.Propofol is currently found to protect neurological function in a variety of models,whereas in the protection of neuronal function after TBI by propofol,nuclear factor E2 related factor 2(Nrf2)-antioxidant reaction(ARE)pathway the mechanism of action remains to be further explored.In view of this,exploring the neuroprotective effect of the drug after TBI can provide a theoretical basis for clinical therapeutic applications after TBI,and may find new therapeutic targets for neurological damage after TBI.ObjectiveTo investigate the protective effects of propofol on neurological function in rats after TBI and its possible related mechanisms of Nrf2-ARE pathway.Methods96 SD rats were randomly divided into sham operation group,sham operation propofol group,TBI group and TBI propofol group,24 rats in each group.The TBI model was prepared by modified Feeney method.The sham-operated propofol group and the TBI propofol group were given propofol 50 mg/kg once daily.The sham operation group and the TBI group were injected with the same amount of normal saline.Modified neurobehavioral functional scores(mNSS)were performed at 1,3,7 and 14 days after injury;dry-wet specific gravity method was used to detect brain water content in injured area;TUNEL staining was used to detect neuronal apoptosis;chemiluminescence was used to detect activity.Oxygen cluster(ROS)content;Western blot analysis of inositol requirement enzyme 1(IRE-1),C/EBP homologous protein(CHOP),heme oxygenase 1(HO-1),NAD(P)H dehydrogenase quinone 1(NQO1)and nuclear factor E2 related factor 2(Nrf2)protein expression.ResultsThere was no significant change in mNSS in the sham operation group and the sham operation propofol group.The scores were basically 0 to 2 points on the 1,3,7 and 14 days.Compared with the sham operation group and the sham operation propofol group,the TBI group and the mNSS of the TBI propofol group was significantly increased(P<0.05).The nerve function recovery of the TBI group was significantly worse than that of the TBI propofol group(9.3±1.4)from 7 days after injury(P<0.05)..Compared with the sham operation group and the sham operation propofol group,the brain water content of the TBI group and the TBI propofol group increased significantly at 1,3,7 and 14 days after injury,and reached the peak at 3 days after injury(P<0.05).Compared with the TBI group,the brain water content of the TBI propofol group was significantly decreased(81.0±0.8)from 3 days after injury(P<0.05).The percentage of apoptotic cells in the sham operation group and the sham operation propofol group was extremely low(range maintained at 2% to 3%)(P<0.05);Compared with the sham operation group and the sham operation propofol group,the TBI group and the TBI propofol group.The apoptosis peak of the phenolic group appeared at 1 day after injury,and remained at a high level at 3,7 and 14 days after injury(P<0.05).Compared with TBI group,7 days after TBI propofol group injury,cells The apoptosis was significantly reduced,and the most significant decrease was the most significant 14 days after injury(14.1±1.4,10.4±1.5)(P<0.05).The ROS content in the sham operation group and the sham operation propofol group was low,ranging from 40 to 45 RFU.Compared with the sham operation group and the sham operation propofol group,the TBI group and the TBI propofol group had the highest ROS content at 1 d after injury.The levels of ROS were still higher at 3,7,and 14 after injury(P<0.05).Compared with the TBI group,the ROS content in the TBI propofol group decreased significantly from 7 days after injury(61.5±4.0)(P<0.05).Compared with the sham operation group and the sham operation propofol group,the expressions of IRE-1 and CHOP were significantly up-regulated in the TBI group and the TBI propofol group(P<0.05),and the expressions of HO-1,NQO1 and Nrf2 in the TBI group were significantly decreased(P< 0.05),the expression of HO-1 and NQO1 in TBI propofol group increased(P<0.05)and the expression of Nrf2 decreased slightly(P<0.05).Compared with TBI group,the expression of IRE-1 and CHOP in TBI propofol group decreased(P<0.05),while the expression of HO-1,NQO1 and Nrf2 was significantly increased(P<0.05).ConclusionPropofol can reduce oxidative stress by activating the Nrf2-antioxidant element(ARE)pathway,reduce brain edema after TBI in rats,inhibit neuronal apoptosis,and play a neuroprotective role.