Effects Of Cholinergic Anti-inflammatory Pathway On Peripheral And Cerebullar Inflammation Induced By Lipopolysaccaride In Rats

Objective To investigate the protective effect of cholinergic anti-inflammatory pathway (CAP) via vagotomy and vagus nerve stimulation during peripheral and cerebullar inflammation induced by lipopolysaccaride in rats.Methods Twenty male healthy rabbits were randomly divided into four equal groups: sham operation (SHAM) group, endotoxemia group (LPS), bilateral cervical vagotomy (VGX) group and vagus nerve stimulation (STM)group . SHAM goup was performed as sham opera tion , LPS group were injected L PS intravenously (10mg/ kg ) ,VGX group were subjected to bilateral cervical vagotomy with administration of LPS. And constant voltage stimuli (5V,2ms,lHZ)were applied to the right cervical vagus nerve trunk of STM group for 20 min immediately with administration of LPS. Blood and tissue samples were collected after two hours in all groups. TNF-a and IL-6 levels of plasma and hippocampus were measured using ELISA. The proliferation and activation of hippocampal astrocytes were investigated with glial fibrillary acidic protein(GFAP) immunohistochemical staining .Results Compared to the SHAM group, The levels of TNF-αand IL-6 in plasma and hippocampus are increased in LPS and VGX group (P<0.05). The number of hippocampal astrocytes were increased and the expression of GFAP were enhanced(P<0.05).Compared to the LPS group, The levels of TNF-αand IL-6 in plasma and hippocampus are significantly increased in VGX group(P<0.05). The number of hippocampal astrocytes were significantly increased and the expression of GFAP were significantly enhanced (P<0.05).While,vagus nerve electrical stimulation inhibited the release of TNF-αand IL-6(P<0.05). The number of hippocampal astrocytes and the expression of GFAP were decreased(P<0.05).Conclusion Cholinergic anti-inflammatory pathway is involved in the regulation of peripheral and cerebullar inflammation,and it depends on the integrity of CAP. Which suggests that vagus nerve play a very important role in regulating the anti–inflammatory. And the activation of hippocampal astrocytes can be effected by CAP.