| Aim: To expound the effects of vagus nerve on the inflammatory response in heart and lung tissues in rats with endotoximia and investigate the role of the cholinergic nervous system in modulating systemic inflammatory response to endotoxin.Methods: Seventy male Wistar rats, weighting 220 20g, were anaesthetized with urethane(25 %, 1.2g-kg-1). The common carotid artery were cannulated and connected to a blood pressure transducer.An acquisition system(Pclab System, Wisinstar CO.BeiJing) was used to monitor mean arterial blood pressure and heart rate continuously. Animals were subjected to bilateral cervical vagtotomy. A bipolar electrodes was placed at the distal end of one side vagus nerve trunk and connected to a stimulation module. The electrical stimulation was controlled by an acquisition system for continuous registration of nerve action potential. Stimuli with constant voltage (5V,2ms,1Hz) were administered at the nerve for 20 min immediately after administration of lipopolysaccharide(LPS, 10mg kg-1,E coli O111:B4, Sigma), and then were repeated 2 times after each of 10 min interval.Rats were randomly divided into 7 groups as follow:(1)sham operation(C, n=10);(2)vagotomy alone(V, n=10);(3)vagus nerve stimulation alone(S, n=10);(4)vagotomy plus vagus nerve stimulation(VS, n=10);(5)LPS injection alone(LPS, n=10);(6)vagotomy plus LPS injection(V-LPS, n=10);(7)vagotomy plus LPS injection and vagus nerve stimulation(VS-LPS, n=10).Blood and tissue pieces from rats heart and lung were collected at 1.5h after LPS administration in all groups. Tumor necrosis factor- a (TNF- ), malondialdehyde (MDA) and myeloperoxidase (MPO) in heart and lung tissues and serum TNF-a , acetylcholine (ACh), CK-MB and corticosterone were determined.Results: (1)Bilateral cervical vagotomy significantly elevated blood pressure , speeded up heart rate and slowed down respiratory rate, but vagus never stimulation reversed changes above. (2)The TNF- a and MDA contents and MPO activity in serum and tissues were very lower in the operation control group and other groups without LPS injection.There were no significant differences in the content of TNF- a and MDA and MPO activity in tissue and CK-MB and corticosterone in serum between each groups without LPS injection. Pathologic lesion was not found in these groups either. (3)LPS administration significantly elevated the levels of TNF- a and ACh and CK-MB and corticosterone in serum and the contents of TNF- a and MDA and MPO in heart and lung tissues. Inflammatory changes including interstitial vascular dilatation and hyperemia and inflammatory cells infiltration were found in heart and lung tissues. (4)Vagotomy without stimulation resulted in significant increase in TNF and MDA contents and MPO activity in tissues as well as TNF- a and CK-MB in serum,but significant decrease in corticosterone and ACh in serum. A more severe inflammatory response than LPSadministration alone in heart and lung tissues was observed. (5)Vagotomy compounded stimulation significantly decreased in TNF-α and MDA and MPO in heart and lung tissues and TNF-α and corticosterone and CK-MB in serum, but increased in ACh in serum. Vagotomy compounded stimulation also atteuated inflammatory response in heart and lung tissues compared with LPS administration alone.Conclusion: (1) Vagus nerve excitation can significantly reduce the levels of proinflammatory mediator and lipid peroxidation product in tissues and serum in endotoxin challenged rats, alleviate the inflammatory response in heart and lung tissues. It might provide a potential protective effect on heart and lung from endotoximia. (2)Vagotomy resulted in significant increase in TNF and MDA contents, and MPO activity in tissues as well as TNF- α and CK-MB in serum and aggravating the inflammatory response in heart and lung tissues. (3)The results suggested that vagus nerve play a very important role in modulating the anti-inflammatory response against endotoxin and preventing tissue from over-inflammatory injury.
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