姜黄素对神经病理性疼痛大鼠脊髓11β羟基固醇脱氢酶1表达的影响

Effect of curcumin on the 11β-hydroxysteroid dehyarogenase 1 expression in spinal cords neuropathic pain rat model

目的探讨皮质醇和11β羟基固醇脱氢酶1(11βHSD1)在神经病理性疼痛大鼠痛觉过敏中的作用,并揭示姜黄素缓解大鼠神经病理性疼痛的作用机制。方法雄性SD大鼠随机分成4组:假手术(Sham)组、坐骨神经慢性压榨损伤模型(CCI)组、CCI+溶剂(SC)组、CCI+姜黄素100 mg/kg(Cur100)组。于术前2 d和术后1、3、5、7、10、14 d测定鼠爪热痛阈(PTWL)和机械痛阈(PMWT),术后3、7和14 d取血,同时取大鼠术侧L4、L5脊髓背角和背根节,用ELISA法测血清皮质醇浓度,用免疫组化法和Western印迹法分析脊髓背角和背根节11βHSD1表达的动态变化。结果与Sham组相比,CCI组大鼠术后1~14d PTWL和PMWT明显降低(P<0.05),血清皮质醇浓度明显升高(P<0.05),术侧脊髓背角和背根节内11βHSD1阳性神经元的表达显著增多(P<0.05)。Cur100大鼠PMWT和PTWL显著提高(P<0.05),同时组大鼠血清皮质醇浓度显著降低(P<0.05),脊髓背角和背根节11βHSD1阳性神经元细胞的表达也明显降低(P<0.05)。结论神经病理性疼痛所致应激引起血清皮质醇浓度升高、脊髓背角和背根节11βHSD1阳性神经元细胞表达增加,姜黄素能减轻CCI大鼠机械性痛觉过敏和热痛觉过敏,降低血清皮质醇浓度及脊髓背角和背根节11βHSD1阳性神经元细胞表达。皮质醇及脊髓背角和背根节的11βHSD1阳性神经元细胞可能与神经病理性疼痛的发病和维持有关。

Objective To observe the effect of stress caused by neuropathic pain on serum cortisol concentration and expression of 11β-hydroxysteroid dehyarogenase 1（11βHSD1）and investigate the action mechanism of curcumin for alleviating neuropathic pain. Methods The 72 male SD rats were randomly divided into 4 groups with 18 rats in each group：sham operation group（Sham）,chronic constrictive injury group（CCI）,solvent contrast group（SC）and curcumin treated group（Cur100）. Curcumin（100 mg/kg/d）was given after the operation in Cur100 group. Paw thermal withdrawal（PTWL）and paw mechanical withdrawal threshold（PMWT）of rats were measured on 2 pre-operative and 1,3,5,7,10,and 14 post-operative days. The animals were deeply anesthetized,the blood was taken from the heart,and the L4-L5 dorsal root ganglion（DRG）of the operated side was removed. The change of cortisol was measured by ELISA and the change of 11βHSD1expression in spinal cord and DRG was determined by immunochemistry and Western blot. Results Compared with sham group,PTWL and PMWT decreased significantly after operation in CCI group（P〈0.01）,serum cortisol concentration was significantly increased（P〈0.01）and the expression of 11βHSD1 was significantly increased in CCI group（P〈0.01）. Compared with CCI group,the PMWT and PTWL was increased in CCI group（P〈0.05）,the serum cortisol concentration was decreased（P〈0.05）and the expression of 11βHSD1was inhibited in Cur100 group（P〈0.05）. Conclusion Stress caused by neuropathic pain triggered the release of cortisol to the blood and increased the expression of 11βHSD1at the same time. Curcumin could alleviate thermal hyperalgesia and mechanical hyperalgesia induced by CCI and could also inhibit the serum cortisol concentration and the expression of 11βHSD1in spinal cord and DRG,which was likely to be related to pathogenesy and maintenance of neuropathic pain.