Effect Of Vagus Nerve Stimulation On Intestinal Barrier Function In Rats With Traumatic Hemorrhagic Shock And Its Association With Remote Lung Injury

[Background and objective]Electrical stimulation of vagus nerve(VNS)can reduce the permeability of the intestinal barrier in rats with traumatic hemorrhagic shock/resuscitation(THS/R),and can also reduce distant organ lung injury.Whether there is a correlation between the two and the specific mechanism are not clear.This study aims to explore the correlation between the protective effect of VNS on intestinal barrier permeability and the protective effect of lung in distant organs.[Materials and methods]Thirty SPF male SD rats aged 8-10 weeks were randomly divided into 5 groups(n=6):THS/R group,VNS group,VNS/C group,VT group and Ctr group.Except for the Ctr group,the rats in the other four groups were exsanguination through the carotid artery to establish the hemorrhagic shock/volume resuscitation model,and the abdominal penetrating incision was made to simulate trauma.Before fluid resuscitation,the rats received right cervical vagus nerve stimulation with a nerve stimulator in group VNS and group VT,and transcutaneous electrical stimulation was used in group VNS/C.The stimulating parameters were set at 1.0mA,1Hz,0.1ms,and the duration of stimulation was 15min.In group VT,abdominal vagotomy was performed before electrical stimulation.At 120 minutes after fluid resuscitation,fluorescein labeled dextran(FD4)was injected into the ileum of the rats to detect intestinal permeability.Thirty minutes later,the rats were sacrificed and specimens were obtained for microscopic observation of intestinal and lung tissue injury,and for determination of blood FD4 and pulmonary surfactant protein-D(SP-D)levels.The expression of Caspase 3,Bcl-2 and Bax in lung tissue and the inflammatory factors TNF-α,IL-6,NF-κB and HMGB-1 in right heart blood,intestinal and lung tissue were also detected.[Result]The intestinal injury scores and barrier permeability in THS/R group,VNS group,VNS/C group and VT group were significantly increased(P<0.05).Both damage score and barrier permeability in VNS group were significantly lower than those in THS/R group(P<0.05);The scores of VNS/C and VT groups were significantly higher than those of VNS group(P<0.05),but there was no significant difference compared with THS/R group(P<0.05).The barrier permeability of VNS group,VNS/C group and VT group was significantly lower than that of THS/R group(P<0.05),but VNS/C group and VT group were significantly higher than VNS group(P<0.05).The mRNA expression levels of TNF-α,IL-6,NF-κB and HMGB-1 in right heart blood,intestinal and lung tissues of THS/R,VNS,VNS/C and VT groups were significantly increased(P<0.05).The expression levels of four inflammatory factors in three sites of VNS group were significantly lower than those of THS/R group,VNS/C group and VT group(P<0.05).The expression levels of apoptotic factors in lung tissues of THS/R group,VNS group,VNS/C group and VT group were up-regulated to varying degrees.The expression levels of Caspase 3 and Bax in VNS group were significantly lower than those in THS/R group,VNS/C group and VT group(P<0.05),but Bcl-2 expression level was significantly higher than THS/R group,VNS/C group and VT group(P<0.05).The lung injury score and blood SP-D content in THS/R,VNS,VNS/C and VT groups were significantly increased(P<0.05).The injury scores of VNS group,VNS/C group and VT group were significantly lower than those of THS/R group(P<0.05),but VNS/C group and VT group were significantly higher than VNS group(P<0.05).The level of SP-D in VNS group was significantly lower than that in THS/R group,VNS/C group and VT group(P<0.05),but there was no significant difference between VNS/C group,VT group and THS/R group(P<0.05).[Conclusion]The protective effect of electrical vagus nerve stimulation on acute lung injury is related to the reduction of intestinal barrier permeability in a rat model of traumatic hemorrhagic shock/volume resuscitation.The mechanism of action is that the increased excitability of vagus nerve reduces the permeability of intestinal barrier,inhibits the production and release of intestinal inflammatory factors,and reduces the level of intestinal inflammatory substances in the lung.Thus,it can down-regulate the NF-κB-mediated inflammatory cascade and the expression of pro-inflammatory cytokines in the lung,ultimately inhibit lung cell apoptosis and alleviate lung tissue injury.