Mitigation of inflammation using the intravenous anesthetic dexmedetomidine in the mouse air pouch model
Mitigation of inflammation using the intravenous anesthetic dexmedetomidine in the mouse air pouch model
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DOI：
10.1080/08923973.2017.1327964
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发表时间：
2017-01-01
影响因子：
3.3
通讯作者：
Kamibayashi, Takahiko
中科院分区：
文献类型：
--
作者：
Inada, Takefumi;Sumi, Chisato;Kamibayashi, Takahiko
右美托咪定是一种α(2)-肾上腺素能/咪唑啉受体激动剂，是一种广泛使用的静脉麻醉药。它目前的主要用途是用于重症监护病房患者的镇静。小鼠气囊模型在研究药物对多种物质诱导的局部炎症的抗炎作用方面具有广泛的用途。在本研究中，使用卡拉胶诱导的气囊炎症模型，我们测试了右美托咪定是否减轻了小鼠气囊局部发生的炎症。我们发现右美托咪定呈剂量依赖性地抑制肿瘤坏死因子(TNF)-α和白介素6(IL)-6的产生，并减少募集到囊袋中的白细胞(WBC)数量。右美托咪定还剂量依赖性地抑制中性粒细胞趋化因子CXCL1和CXCL2的产生。此外，囊内注射CXCL1/cxCl2，但不能逆转肿瘤坏死因子-α或白介素6，可成功逆转右美托咪定引起的WBC向囊袋内募集的减少。育亨宾可逆转右旋美托咪定对细胞因子和趋化因子产生的抑制作用，提示右旋美托咪定的抗炎作用主要是通过刺激α(2)-肾上腺素能受体实现的。结论：右旋美托咪定在角叉菜胶诱导的小鼠气囊炎模型中具有抗炎作用，其抑制中性粒细胞趋化因子CXCL1和CxCL2的产生可能至少部分与抑制WBC囊内募集有关。
Dexmedetomidine, an alpha(2)-adrenergic/imidazoline receptor agonist, is a widely used intravenous anesthetic. Its primary current usage is for sedation of patients in the intensive care unit. The mouse air pouch model is versatile in studying the anti-inflammatory effect of a drug on a local inflammation, which is induced by a variety of substances. In the present study, using the carrageenan-induced air pouch inflammation model, we tested whether dexmedetomidine mitigates inflammation occurring locally in the mouse air pouch. We found that dexmedetomidine dose-dependently inhibited the production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in the pouch and decreased the number of white blood cells (WBC) recruited into the pouch. Dexmedetomidine also dose-dependently inhibited the production of neutrophil chemokines, cxcl1 and cxcl2. Furthermore, the dexmedetomidine-induced decreased recruitment of WBC into the pouch was successfully reversed with intra-pouch administration of cxcl1/cxcl2, but not TNF-alpha or IL-6. Lastly, the inhibition of the production of the cytokines and chemokines with dexmedetomidine was reversed by the treatment of yohimbine, suggesting that dexmedetomidine's anti-inflammatory effect is primarily via the stimulation of the alpha(2)-adrenergic receptor. We conclude that dexmedetomidine has an anti-inflammatory property in the carrageenan-induced mouse air pouch inflammation model, and that the dexmedetomidine-induced inhibition of production of the neutrophil chemokines, cxcl1 and cxcl2, may be related, at least in part, to the inhibition of WBC intra-pouch recruitment.