Protection Of Polydatin On Neuronal Mitochondria Damage And Lung Injury After Traumatic Brain Injury

BackgroundTraumatic brain injury(TBI)has a high morbidity and mortality rate,and more common complications,such as secondary brain injury and lung injury,could increase the mortality rate of patients.Secondary brain injury that induced by a series of pathophysiological reactions after TBI is defined as mitochondrial damage in peripheral neurons which finally could cause apoptosis.It is reported that ER stress,p38 MAPK and oxidative stress are involved in the mechanisms of secondary brain injury.Some literatures have shown that up-regulation of SIRTI expression and activity can affect the mechanisms above,which could protect neuronal mitochondria.Secondly,the mechanisms of inflammation of lung after TBI is mainly related to oxidative stress and inflammation stress[10.11.12].The polydatin(PD)mentioned in this paper can act as a receptor agonist of SIRT1 and plays an important role in anti-oxidative stress reaction and anti-inflammatory reaction in other tissues.Therefore,we hypothesize that PD could protect neurons mitochondria and lung after TBI.Objective:(1)Whether PD exerts neuroprotective effects during TBI secondary brain injury by up-regulating SIRT1.(2)The protective effect of PD on secondary lung injury after TBI.MethodMale Sprague-Dawley rats(body weight 220-250 g)were housed individually under controlled environmental conditions for a 12 hour light/dark cycle with no restriction on food and water throughout the study.Animals were purchased from the Experimental Animal Center of Guangzhou Southern Medical University,China.Anesthesia was performed using a mixture of 13.3%carbamate and 0.5%chloralose(0.65 mL/100 g body weight,intraperitoneally).Secondary brain injury group:Sham group,TBI group,TBI + SRT1720 and TBI + PD group.(n = 6/group).The injured lateral cortex of the rat brain was isolated 6 hours after TBI.Secondary lung injury group:Sham group,sham+PD group,TBI group,TBI+PD)group(n=10/group).Rat lung tissue was isolated 6 hours after TBI.The TBI model was made by hydraulic shock method,and PD[15]30 mg/kg and SRT 1720[22](20 mg/kg)were injected immediately after shock.Sham-operated rats underwent the same preparation procedure,including craniotomy but no injuries.Result.Group of secondary brain injury:PD promotes expression of SIRT1 after TBI.PD inhibits oxidative stress which inhibits ROS accumulation in mitochondrial.Neuronal mitochondrial damage is alleviated by PD after TBI.PD inhibits the collapses of mitochondrial membrane potential(MMP)after TBI.PD inhibits p38 MAPK signaling and mitochondrial apoptosis pathways.PD inhibits reaction of ER stress after TBI.PD reduces neurological scores and improves survival rates in rats(all P values above<0.05).Group of secondary lung injury:PD could alleviate the pathological damage of the lung after TBI.PD attenuates the dry-to-wet weight ratio in lung tissues of TBI rats.PD inhibits oxidative stress in the lung of TBI rats.PD inhibits the release of inflammatory mediator in TBI rats.PD reduces protein content,the total number of cells,and percentage of neutrophils in alveolar lavage fluid.(The above P values are all<0.05).Conclusion:PD may promote SIRT1 expression which may be a key point to inhibit p38 pathway,ER stress,ROS aggregation to exert its protection of Neuron Mitochondrial.In addition,PD can alleviate secondary lung injury in TBI rats,and its mechanism may be related to reactions of anti-oxidative stress and anti-inflammatory.