Effects Of Cholinergic Anti-inflammatory Pathway On Lung Ischemia-Reperfusion Injury

Objective: To investigate the protective effect of cholinergic anti-inflammatory pathway (CAP) via vagotomy, vagus nerve stimulation and acetylcholinesterase inhibitors during lung ischemia-reperfusion injury.Methods: 35 male healthy rabbits were randomly divided into five equal groups: sham operation (SHAM) group, ischemia reperfusion (IR) group, bilateral cervical vagotomy (VGX) group, vagus nerve stimulation (STM) group and tacrine (THA) group. Rabbits were anaesthetized and subjected to mechanical ventilation. The right carotid artery was cannulated to monitor MAP and HR. The bilateral cervical vagus nerve trunks and hilum of left lung were exposed and isolated from surrounding tissue. THA group was administered with tacrine (3mg/Kg, i.v.), other groups receiving saline (0.9%). The animals were blocked hilum of left lung for 60 minutes except the SHAM group. VGX group was subjected to bilateral cervical vagotomy, and constant voltage stimuli (5V,2ms,lHZ)were applied to the left cervical vagus nerve trunk of STM group for 20 min immediately after loosing the clamp. Blood and tissue samples were collected after reperfusion for 120 minutes in all groups. TNFa levels of plasma, heart, liver and left lung were measured using ELISA. The NF-kB P⁶⁵ activity of left lung was determined by using Western Blot Analysis. The results were also received about the activity of MPO, wet to dry ratio (W/D) of left lung and content of plasma cortisol. The histopathologic changes of lung tissue were assessed by using HE dyeing.Results: After reperfusion, IR and VGX groups produced progressive hypotension. The MAP change Ratios of VGX group were lower than those of IR group after reperfusion 50min, but THA remarkably attenuated the development of hypotension at 80min after reperfusion. PH, PaO₂ and SaO₂ were fallen significantly subjected to VGX procedures; STM and THA reverted the value of blood gas. Vagotomy caused a farther increase of serous TNF compared with IR group; STM observably inhibited pulmonary and hepatic TNF, and THA effectively attenuated TNF expression in heart, liver and left lung. VGX group had a higher NF-κB P⁶⁵ level than IR group, STM and THA can markedly modify the rise. STM and THA prevented the increases of activity of MPO and W/D value caused by IR, but VGX...