| Objective To investigate the effect of the cholinergic anti-inflammatory pathway on hemadynamics and the level of serum tumor necrosis factor a(TNFα) and liver nuclear factor kappa B(NFkB) in septic and haemorrhagic shock in rats.Methods The septic shock part: Septic shock was induced by cecal ligation and puncture(CLP). Thirty male Sprague-Dawley rats were randomly divided into six groups: SHAM groups were subjected to sham surgery, CLP groups were subjected to CLP and a comparable sham surgical procedure in which the vagal trunks were exposed and isolated from the surrounding tissue but not transected, VGX groups were subjected to bilateral cervical vagotomy following CLP, STM groups were subjected to bilateral cervical vagotomy after CLP and the left vagus nerve trunk was placed across bipolar platinum electrodes connected to a stimulation module and controlled by an acquisition system, THA groups were administered THA(1.5mg/kg) via intravenous routes after subjected to bilateral cervical vagotomy, a-BGT groups were administered a-bungarotoxin(1.0ug/kg) via intravenous routes before electrical stimulation of the vagus nerve. Constant voltage stimuli(5V,2ms,1Hz) were applied to the nerve for 20 minutes immediately after the models were operated. The haemorrhagic shock part: Haemorrhagic shock was induced by intermittent withdrawing of blood until mean arterial pressure stabilized within the range of 35 to 40 mmHg. Thirty male Sprague-Dawley rats were randomly divided into six groups: SHAM group, Hem group, VGX group, STM group, THA group and a-BGT group. The left vague nerve trunk was placed across bipolar platinum electrodes connected to a stimulation module and controlled by an acquisition system. Stimuli with constant voltage (5V,2ms,1Hz) were applied to the nerve for 12 minutes, starting 5 minutes after MAP stabilized at a level of 35 to 40 mmHg. Before stimulation the common carotid artery was implanted into a blood pressure transducer for continuous registration of mean arterial blood pressure (MAP). Blood samples and liver samples of these rats were collected in all groups after stimulation. Serum TNFα and liver NFkB was determined.Results The septic shock part: the MAP gradully decreased and the amount of serum TNFα and NFkB significantly increased after CLP alone or with bilateral cervical vagotomy compared with sham-operated controls. Application of constant voltage pulses to the caudal vagus trunks significantly prevented the development of CLP-induced hypotension and reduced serum TNFα, but have no effect on the level of liver NFkB. THA (1.5mg/kg,i.v.) administration after bilateral cervical vagotomy reversed hypotension and attenuated serum TNFα, also have no effect on the level of liver NFkB. a-bungarotoxin(1.0ug/kg,i.v.) pretreatment significantly reversed the inhibitory effect of vagal stimulation, but have no effect on the level of liver NFkB. The haemorrhagic shock part: MAP was markedly impaired at the ending of bleeding, and the amount of serum TNFα and liver NFkB markedly increased 45 minutes after the bleeding was discontinued. Bilateral cervical vagotomy did not significantly modify the rise in serum TNFα and slightly increased liver NFkB activation. Application of constant voltage pulses to the caudal vagus trunks significantly reduced serum TNFα and blunted liver NFkB activation. THA(1.5mg/kg,i.v.) administration after bilateral cervical vagotomy reversed hypotension and attenuated serum TNFα and liver NFkB amounts, But a-bungarotoxin (1.0ug/kg,i.v.) pretreatment reverted the inhibitory effects of vagal stimulation.Conclusions The results suggested that the cholinergic anti-inflammatory pathway might produce a potential protective effect on septic and haemorrhagic shock in rats. The pathway can inhibit the release of inflammatory cytokines significantly and rapidly and attenuate systemic inflammatory response. The inhibitory effect is mediated primarily by a-bungarotoxin-sensitive, nicotinic acetycholine receptor ^ subunit. There are some differences between septic and... |
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