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

Objective To investigate the effect and mechanism of vagotomy, vagus nerve stimulation and electro-acupuncture at Zusanli points against the lung ischemia-reperfusion injury of rabbits.Methods The part of vagus nerve stimulation: 36 male healthy rabbits were randomly divided into four equal groups:①sham operation (SHAM) group,②ischemia reperfusion (IR) group,③bilateral cervical vagotomy (VGX) group,④vagus nerve stimulation (STM) group. The bilateral cervical vagus nerve trunks and hilum of left lung were exposed and isolated from surrounding tissue. 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, 1Hz) were applied to the left cervical vagus nerve trunk of STM group for 20 min immediately after loosing the clamp. The part of electro-acupuncture at Zusanli points: A, B and E group were as same as the first part. Twenty-one healthy male New Zealand white rabbits weighting (2.5±0.5)kg were randomly divided into other three groups: Non-acupoints+ischemia -reperfusion (group C): left hilum was isolated and clamped for 60min, after declamping the lungs electro-acupuncture the non-acupoints for 30min and the lungs were ventilated for another 90min; Electro-acupuncture to"ZuSanLi"Points+ischemia-reperfusion (group D): left hilum was isolated and clamped for 60min, after declamping the lungs electro-acupuncture the"ZuSanLi"Points for 30min and the lungs were ventilated for another 90min; Bilateral cervical vagotomy+ electro-acupuncture to"ZuSanLi"Points+ischemia-reperfusion (group F): left hilum was isolated and clamped for 60min, before declamping the lungs, the animals were subjected to bilateral cervical vagotomy and electro-acupuncture the"ZuSanLi"Points for 30min and the lungs were ventilated for another 90min. The common carotid artery were implanted into a blood pressure transducer for continuous registration of mean arterial blood pressure (MBP).Left lung was excised for measurement of MDA﹑MPO﹑TNFαcontent and NFκB activity and wet-dry ration(W/D) and histopathologic changes. Blood samples of these rabbits were collected after the operation complete for measurement of TNFαcontent and blood gas analysis.Results The part of vagus nerve stimulation: The MAP change Ratios of VGX group were lower than those of IR group subsequent to 50min reperfusion. pH, PaO2 and SaO2 values of VGX group decreased substantially as compared with those of IR group; STM group produced opposite result. Vagotomy caused a farther increase of serous TNF in VGX group as compared with IR group. Whereas STM group observably inhibited pulmonary and hepatic TNF. VGX group had a higher NFκB P65 level than IR group, STM group can markedly modify the rise. STM group prevented the increases of activity of MPO and W/D value caused by IR, but VGX group aggravated those rises. As compared with IR group, STM group suppressed inflammatory responses, and pathological depravation was induced by vagotomy. The part of electro-acupuncture at Zusanli points: As compared with A groups, B groups produced a remarkable increase of lung MPO,MDA﹑TNFαcontent and NFκB activity, and lead to acidosis and hypoxia and pathological depravation. C groups showed no difference as compared with B groups in statistical manner. On the contrary, D groups attenuated significantly lung MPO,MDA﹑TNFαcontent and effectively inhibited NFκB activity and reverted the value of blood gas and pathological changes. E groups offered a significantly increase in lung MPO,MDA﹑TNFαcontent and NFκB activity and W/D ration, and lead to acidosis and hypoxia and pathological depravation as compared with B groups. F groups offered same results as E groups as compared with D groups, and showed no difference as compared with E groups in statistical manner.Conclusions Vagotomy can interdict cholinergic anti-inflammatory pathway and aggravate lung ischemia-reperfusion injury. Vagus nerve stimulation and electro-acupuncture at Zusanli points can protect the lung against ischemia-reperfusion injury via activating cholinergic anti-inflammatory pathway. The mechanisms that CAP alleviated lung ischemia-reperfusion injury were likely to inhibit the leukocyte aggregation and activity, suppress NFκB and TNFαexpression.