Astrocytes respond to all forms of central nervous system (CNS) insults by a process referred to as reactive astrogliosis. Inhibition of astrocyte growth and activation is an important strategy for promoting injured CNS repair. STAT3 (signal transducer and activator of transcription 3) is reported to be a critical regulator of astrogliosis, and resveratrol (RES, a dietary polyphenol) is considered to be a natural inhibitor of STAT3 expression and phosphorylation. In this study, we investigated the effects of RES on STAT3 expression and phosphorylation, and then on the proliferation and activation of astrocytes, a critical process in reactive astrogliosis, in rat primary cultured astrocytes and an in vitro scratch-wound model. RES downregulated the expression levels of STAT3, P-STAT3 and GFAP (glial fibrillary acidic protein) in cultured astrocytes. The positive index of Ki67 was apparently reduced in cultured astrocytes after RES treatment. Meanwhile, cultured astrocyte proliferation and activation were attenuated by RES. Moreover, in the established in vitro scratch-wound model the increased expression levels of STAT3, P-STAT3 and GFAP induced by scratching injury were also clearly inhibited by RES. In addition, the inhibitory effect of RES on cell proliferation was similar to that of AG490 (a selective inhibitor of STAT3 phosphorylation) and abrogated by Colivelin (a STAT3 activator) stimuli. Taken together, our data suggest that RES is able to inhibit reactive astrocyte proliferation and activation mainly via deactivating STAT3 pathway. So RES may have a therapeutic benefit for the treatment of the injured CNS.

中文翻译：

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白藜芦醇下调大鼠原代星形胶质细胞培养物中的STAT3表达和星形胶质细胞激活。

星形胶质细胞通过一种称为反应性星形胶质增生的过程对各种形式的中枢神经系统（CNS）损伤作出反应。抑制星形胶质细胞的生长和激活是促进受损中枢神经系统修复的重要策略。据报道，STAT3（信号转导和转录激活因子3）是星形胶质增生的关键调节剂，白藜芦醇（RES，一种膳食多酚）被认为是STAT3表达和磷酸化的天然抑制剂。在这项研究中，我们研究了RES对STAT3表达和磷酸化的影响，然后对星形胶质细胞的增殖和活化，反应性星形胶质增生的关键过程，大鼠原代培养的星形胶质细胞和体外刮伤模型的影响。RES下调了星形胶质细胞中STAT3，P-STAT3和GFAP（胶质纤维酸性蛋白）的表达水平。RES处理后，培养的星形胶质细胞中Ki67的阳性指数明显降低。同时，RES减弱了培养的星形胶质细胞的增殖和活化。而且，在建立的体外刮伤模型中，RES也明显抑制了由刮伤引起的STAT3，P-STAT3和GFAP表达水平的增加。此外，RES对细胞增殖的抑制作用与AG490（STAT3磷酸化的选择性抑制剂）相似，但被Colivelin（STAT3激活剂）刺激消除。两者合计，我们的数据表明，RES能够主要通过失活STAT3途径抑制星形胶质细胞的增殖和活化。因此，RES对于治疗受伤的CNS可能具有治疗益处。