Ketamine suppresses intestinal NF-kappa B activation and proinflammatory cytokine in endotoxic rats

氯胺酮抑制内毒素大鼠肠道 NF-κB 活化和促炎细胞因子

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作者:Jie Sun, Xiao-Dong Wang, Hong Liu, Jian-Guo Xu

Aim

To investigate the protective effect of ketamine on the endotoxin-induced proinflammatory cytokines and NF-kappa B activation in the intestine.

Conclusion

Ketamine can suppress endotoxin-induced production of proinflammatory cytokines such as TNF-alpha and IL-6 production in the intestine. This suppressive effect may act through inhibiting NF-kappa B.

Methods

Adult male Wistar rats were randomly divided into 6 groups: (a) normal saline control, (b) challenged with endotoxin (5 mg/kg) and treated by saline, (c) challenged with endotoxin (5 mg/kg) and treated by ketamine (0.5 mg/kg), (d) challenged with endotoxin (5 mg/kg) and treated by ketamine (5 mg/kg ), (e) challenged with endotoxin (5 mg/kg) and treated by ketamine (50 mg/kg), and (f) saline injected and treated by ketamine (50 mg/kg). After 1, 4 or 6 h, TNF-alpha and IL-6 mRNA were investigated in the tissues of the intestine (jejunum) by RT-PCR. TNF-alpha and IL-6 were measured by ELISA. We used electrophoretic mobility shift assay (EMSA) to investigate NF-kappa B activity in the intestine.

Results

NF-kappa B activity, the expression of TNF-alpha and IL-6 were enhanced in the intestine by endotoxin. Ketamine at a dose of 0.5 mg/kg could suppress endotoxin-induced TNF-alpha mRNA and protein elevation and inhibit NF-kappa B activation in the intestine. However the least dosage of ketamine to inhibit IL-6 was 5 mg/kg in our experiment.

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