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氯诺昔康的剂量相关性抗炎/镇痛作用:大鼠脊髓c-Fos蛋白研究

Dose-related anti-inflammatory/analgesic effects of lornoxicam: a spinal c-Fos protein study in the rat.

作者信息

Buritova J, Besson J M

机构信息

Unité de Recherche de Physiopharmacologie du Système Nerveux, INSERM U. 161 and EPHE, Paris, France.

出版信息

Inflamm Res. 1998 Jan;47(1):18-25. doi: 10.1007/s000110050245.

Abstract

OBJECTIVE

To evaluate the anti-inflammatory/analgesic effects of lornoxicam in the carrageenan model of inflammatory nociception.

MATERIAL AND METHODS

Three hours after intraplantar carrageenan (6 mg/150 microl of saline), we assessed the effects of pre-administered lornoxicam (0.1, 0.3, 1, 3 and 9 mg/kg i.v., n=10 rats for each group) on both the peripheral oedema and number of c-Fos-protein-like immunoreactive (c-Fos-LI) neurons in the lumbar L4-L5 segments, in the awake rat.

RESULTS

Lornoxicam dose-relatedly reduced both the carrageenan evoked oedema (r=0.63 and r=0.53 for paw and ankle diameter respectively; p<0.001 for both) and total number of spinal c-Fos-LI neurons (r=0.79; p<0.001), with the strongest effect corresponding to a 75 +/- 2% reduction of the number of c-Fos-LI neurons (p<0.001) for the highest dose (9 mg/kg), and a 45 +/- 3% reduction (p<0.001) for the low dose of 0.3 mg/kg. Reductions of both the peripheral oedema and spinal c-Fos expression were correlated (r=0.74 and r=0.57 for the paw and ankle diameter respectively; p<0.001 for both).

CONCLUSIONS

Our results demonstrate that lornoxicam reduces in parallel both the carrageenan-evoked oedema and spinal c-Fos expression, with clear evidence for a potent effect of low doses of lornoxicam. Correlated reductions in c-Fos expression and paw oedema suggest a predominantly peripheral site of action of lornoxicam.

摘要

目的

在角叉菜胶诱发的炎性伤害感受模型中评估氯诺昔康的抗炎/镇痛作用。

材料与方法

在足底注射角叉菜胶(6毫克/150微升生理盐水)3小时后,我们评估预先给予氯诺昔康(0.1、0.3、1、3和9毫克/千克静脉注射,每组n = 10只大鼠)对清醒大鼠外周水肿以及腰4 - 腰5节段中c-Fos蛋白样免疫反应性(c-Fos-LI)神经元数量的影响。

结果

氯诺昔康剂量依赖性地减轻角叉菜胶诱发的水肿(爪部和踝部直径的r分别为0.63和0.53;两者p均<0.001)以及脊髓c-Fos-LI神经元总数(r = 0.79;p<0.001),最高剂量(9毫克/千克)时对c-Fos-LI神经元数量减少作用最强,减少了75±2%(p<0.001),低剂量0.3毫克/千克时减少了45±3%(p<0.001)。外周水肿和脊髓c-Fos表达的降低具有相关性(爪部和踝部直径的r分别为0.74和0.57;两者p均<0.001)。

结论

我们的结果表明氯诺昔康同时减轻角叉菜胶诱发的水肿和脊髓c-Fos表达,有明确证据表明低剂量氯诺昔康有强效作用。c-Fos表达和爪部水肿的相关降低提示氯诺昔康主要作用于外周部位。

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