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姜黄素通过抑制慢性缩窄性损伤大鼠模型脊髓背角星形胶质细胞的激活和细胞内外信号调节激酶信号通路发挥抗伤害作用。

Curcumin exerts antinociceptive effects by inhibiting the activation of astrocytes in spinal dorsal horn and the intracellular extracellular signal-regulated kinase signaling pathway in rat model of chronic constriction injury.

机构信息

Department of Anatomy and Neurobiology, Zhongshan Medical School of Sun Yat-sen University, Guangzhou, Guangdong 510120, China.

出版信息

Chin Med J (Engl). 2013 Mar;126(6):1125-31.

Abstract

BACKGROUND

Activation of glial cells and the extracellular signal-regulated kinase (ERK) signaling pathway play an important role in the development and maintenance of neuropathic pain. Curcumin can alleviate the symptom of inflammatory pain by inhibiting the production and release of interleukin and tumor necrosis factor. However, whether curcumin affects neuropathic pain induced by nerve injury and the possible mechanism involved are still unknown. This study investigated the effects of tolerable doses of curcumin on the activation of astrocytes and ERK signaling in the spinal dorsal horn in rat model of neuropathic pain.

METHODS

Adult male Sprague-Dawley rats were randomly divided into three groups: a control (sham operated) group, and chronic constriction injury groups (to induce neuropathic pain) that were either untreated or treated with curcumin. Thermal and mechanical hyperalgesia thresholds were measured. The distribution and morphological changes of astrocytes were observed by immunofluorescence. Western blotting was used to detect changes in the expression of glial fibrillary acid protein (GFAP) and phosphorylated ERK.

RESULTS

Injured rats showed obvious mechanical allodynia and thermal hyperalgesia. The number of GFAP-positive astrocytes, and the fluorescence intensity of GFAP were significantly increased in the spinal dorsal horn of injured compared with control rats. The soma of astrocytes also appeared hypertrophied in injured animals. Expression of GFAP and phosphorylated ERK was also significantly increased in the spinal dorsal horn of injured compared with control rats. Curcumin reduced the injury-induced thermal and mechanical hyperalgesia, the increase in the fluorescence intensity of GFAP and the hypertrophy of astrocytic soma, activation of GFAP and phosphorylation of ERK in the spinal dorsal horn.

CONCLUSIONS

Curcumin can markedly alleviate nerve injury-induced neuropathic pain in rats. The analgesic effect of curcumin may be attributed to its inhibition of astrocyte hypertrophy in the spinal dorsal horn and phosphorylation of the ERK signaling pathway.

摘要

背景

胶质细胞的激活和细胞外信号调节激酶(ERK)信号通路在神经病理性疼痛的发生和维持中起着重要作用。姜黄素通过抑制白细胞介素和肿瘤坏死因子的产生和释放,可以缓解炎症性疼痛的症状。然而,姜黄素是否影响神经损伤引起的神经病理性疼痛以及可能涉及的机制尚不清楚。本研究探讨了耐受剂量的姜黄素对神经病理性疼痛大鼠模型脊髓背角星形胶质细胞激活和 ERK 信号的影响。

方法

成年雄性 Sprague-Dawley 大鼠随机分为三组:对照组(假手术)和慢性缩窄性损伤组(诱导神经病理性疼痛),未治疗或用姜黄素治疗。测量热和机械性痛觉过敏阈值。通过免疫荧光观察星形胶质细胞的分布和形态变化。Western blot 检测胶质纤维酸性蛋白(GFAP)和磷酸化 ERK 的表达变化。

结果

损伤大鼠表现出明显的机械性痛觉过敏和热痛觉过敏。与对照组相比,损伤大鼠脊髓背角 GFAP 阳性星形胶质细胞数量和 GFAP 荧光强度明显增加,星形胶质细胞体也出现肥大。与对照组相比,损伤大鼠脊髓背角 GFAP 和磷酸化 ERK 的表达也明显增加。姜黄素减轻了损伤引起的热痛觉过敏和机械性痛觉过敏,减少了 GFAP 荧光强度的增加和星形胶质细胞体的肥大,抑制了脊髓背角 GFAP 的激活和 ERK 的磷酸化。

结论

姜黄素能明显减轻大鼠神经损伤引起的神经病理性疼痛。姜黄素的镇痛作用可能与其抑制脊髓背角星形胶质细胞肥大和 ERK 信号通路磷酸化有关。

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