Electrically Vagal Nerve Stimulation Protects Intestinal Epithelial Glycocalyx After Traumatic Hemorrhagic Shock By Activating Cholinergic Anti-inflammatory Pathway

[Background and purpose]Traumatic Hemorrhagic shock(THS)is one of the leading causes of morbidity and mortality of working age people worldwide,and fluid resuscitation is one of the effective treatments.Traumatic hemorrhagic shock/liquid resuscitation(THS/R)could cause intestinal mucosal injury and increase gut permeability,which could induce systemic inflammatory response and multiple organ failure.Studies shown that vagal nerve stimulation(VNS)could decrease gut permeability after THS/R and alleviate systemic inflammatory response and multiple organ failure,but the specific mechanism is unclear.Glycocalyx covers the surface of enterocytes,which is important for building up of the intestine barrier.However,the effect of VNS on intestinal epithelial glycocalyx in the process of THS/R is still unknown.Thus,the purposes of this study were to explore the change of intestinal epithelial glycocalyx during THS/R,and the effect of VNS on intestinal epithelial glycocalyx and its mechanism.[Materials and methods]Male Sprague Dawley rats were randomly divided into sham surgery group(SS group),traumatic hemorrhagic shock/fluid resuscitation group(THS/R group),traumatic hemorrhagic shock/fluid resuscitation+vagal nerve stimulation(THS/R+VNS group),and traumatic hemorrhagic shock/fluid resuscitation+vagal nerve stimulation+ Methyllycaconitine(THS/R+V SM group).Rats were anesthetized and exposed cervical nerve.Besides SS group,rats in the other three groups were made the traumatic hemorrhagic shock model by withdrawing blood from the common carotid artery,and the mean arterial pressure was maintained between 30 and 35 mmHg for 60 minutes,then the fluid resuscitation was performed.Rats in THS/R+VNS and THS/R+VSM group were received cervical vagal nerve stimulation before fluid resuscitation,and THS/R+VSM group were also injected methyllycaconitine to block cholinergic anti-inflammatory pathway.The intestinal epithelial glycocalyx was detected by immunofluorescence.Intestinal permeability,gut and lung injury and inflammation factors were assessed.[Results]Intestinal epithelial glycocalyx and gut tissue were damaged obviously in THS/R group.Compared with THS/R group,the intestinal epithelial glycocalyx damage alleviated,the intestinal permeability decreased by 43%,the levels of IL-6、TNF-α、NF-κB and MPO were downregulated and the IL-10 level was upregulated in THS/R+VNS group(P<0.05).In addition,the pulmonary vascular permeability was decreased,lung tissue injury was relieved,and inflammatory factors levels were decreased(P<0.05)in THS/R+VNS group.However,compared with THS/R+VNS group,the intestinal epithelial glycocalyx damage and gut and lung injury were deteriorated,and the inflammation factors levels in gut and lung tissue were increased in THS/R+VSM group(P<0.05).[Conclusions]This experiment demonstrated that traumatic hemorrhagic shock/liquid resuscitation could damage intestinal epithelial glycocalyx,and vagal nerve stimulation could relieve the intestinal epithelial glycocalyx damage,alleviate gut and lung injury,and inhibit inflammation response in gut and lung tissues by cholinergic anti-inflammatory pathway.