Abstract:

AIM: To elucidate the anti-inflammatory mechanism of dexmedetomidine through the cholinergic anti-inflammatory pathway.  METHODS: BALB/c mice were selected as the experimental animals and were intraperitoneally injected with LPS (10 mg/kg, injection time longer than 2 min) to establish the mouse model of endotoxemia. Dexmedetomidine was applied to intervene. 60 mice were divided into three groups （20 in each）in the behavioural performance and living conditions experiment, i.e. the dexmedetomidine group (Dex group), normal saline group (Saline group) and blank control group (C group). Behavioural performance and survival rate of the three groups were observed 120 hours after drug intervention. Mice were divided into four groups with 16 in each group in the detection of serum inflammatory factors and observation of the pathological morphology, i.e. physiological saline (Saline group) and dexmedetomidine group (Dex group) alpha bungarotoxin+dexmedetomidine group (alpha BGT+Dex group) and blank control group (C group) . Enzyme linked immunosorbent assay was used to detect the concentration of serum TNF-a, IL-1β and IL-6. Pathological examination was performed thereafter. Mice were divided into two groups with 16 in each group for the cervical vagectomy experiment, i.e. sham operation group (SHAM+Dex group) and cervical vagectomy group (VNX+Dex group). Concentration of serum TNF-a, IL-1 and IL-6 three hours after LPS injection were detected.RESULTS:In the survival analysis experiment, the survival rate of dexmedetomidine group was significantly higher than that of the endotoxemia group (P<0.01). Pre-emptive administration of dexmedetomidine significantly attenuated the cytokine response after endotoxin-induced endotoxemia (P<0.01). Moreover, there were significant differences in changes of heart tissue, liver tissue, kidney tissue and lung tissue. Expression levels of TNF-a, IL-1β, IL-6 in the VNX+Dex group were significant higher than those in the SHAM + Dex group (P<0.01). CONCLUSION:Pre-emptive administration of dexmedetomidine increases the activity of cervical vagus nerve and can improve survival rate in experimental endotoxemia by inhibiting the inflammatory cytokines release.

Key words: cytokine, dexmedetomidine, endotoxemia