Wang Lin-Lin, Shi Dong-Ling, Gu Hui-Yao, Zheng Ming-Zhi, Hu Jue, Song Xing-Hui, Shen Yue-Liang, Chen Ying-Ying
Department of Physiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
Mol Med Rep. 2016 May;13(5):4051-7. doi: 10.3892/mmr.2016.5027. Epub 2016 Mar 21.
The present study aimed to investigate the effect of resveratrol on inflammatory pain. Mice were injected intraperitoneally with lipopolysaccharide (LPS) for 5 consecutive days to induce subacute systemic inflammation. Acetic acid‑induced writhing tests and tail‑flick tests were performed following the final LPS injection. Glial fibrillary acidic protein (GFAP; an astrocyte‑specific activation marker), ionized calcium binding adapter molecule 1 (Iba‑1; a microglia‑specific activation marker) and sirtuin 1 (SIRT1) protein expression levels were detected using immunohistochemistry analysis or western blotting. Following administration of LPS for 5 days, the number of writhes increased and the tail‑flick latency decreased. Resveratrol (10 or 20 mg/kg) partly inhibited LPS‑induced hyperalgesia and prevented the increase in tumor necrosis factor‑α and interleukin 6 levels induced by LPS. LPS injection reduced the SIRT1 protein expression and increased the number of GFAP‑positive and Iba‑1‑positive cells in the spinal cord. Resveratrol increased the SIRT1 protein expression levels and decreased the number of GFAP‑positive and Iba‑1‑positive cells in LPS‑treated mice. The protective effect of resveratrol was partly blocked by a selective SIRT1 inhibitor, EX‑257. Results from the present study suggest that subacute treatment with LPS induced the activation of glial cells and hyperalgesia. Resveratrol was demonstrated to inhibit the activation of glial cells and attenuate inflammatory hyperalgesia in a SIRT1‑dependent manner.
本研究旨在探讨白藜芦醇对炎性疼痛的影响。连续5天腹腔注射脂多糖（LPS）诱导小鼠发生亚急性全身炎症。在最后一次注射LPS后进行乙酸诱导的扭体试验和甩尾试验。采用免疫组织化学分析或蛋白质印迹法检测胶质纤维酸性蛋白（GFAP，一种星形胶质细胞特异性激活标志物）、离子钙结合衔接分子1（Iba-1，一种小胶质细胞特异性激活标志物）和沉默调节蛋白1（SIRT1）的蛋白表达水平。给予LPS 5天后，扭体次数增加，甩尾潜伏期缩短。白藜芦醇（10或20 mg/kg）部分抑制LPS诱导的痛觉过敏，并阻止LPS诱导的肿瘤坏死因子-α和白细胞介素6水平升高。注射LPS可降低脊髓中SIRT1蛋白表达，并增加GFAP阳性和Iba-1阳性细胞数量。白藜芦醇可增加LPS处理小鼠的SIRT1蛋白表达水平，并减少GFAP阳性和Iba-1阳性细胞数量。白藜芦醇的保护作用部分被选择性SIRT1抑制剂EX-257阻断。本研究结果表明，LPS亚急性处理可诱导胶质细胞激活和痛觉过敏。白藜芦醇被证明以SIRT1依赖的方式抑制胶质细胞激活并减轻炎性痛觉过敏。
