Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Neuroscience Research Center of Changzheng Hospital, Second Military Medical University, Shanghai 200433, China.
Glia. 2010 Jun;58(8):901-15. doi: 10.1002/glia.20972.
Spinal cord injury (SCI) is a cause of major neurological disability, and no satisfactory treatment is currently available. Traumatic SCI directly damages the cell bodies and/or processes of neurons and triggers a series of endogenous processes, including neuroinflammatory response and reactive astrogliosis. In this study, we found that triptolide, one of the major active components of the traditional Chinese herb Tripterygium wilfordii Hook F, inhibited astrogliosis and inflammation and promoted spinal cord repair. Triptolide was shown to prevent astrocytes from reactive activation by blocking the JAK2/STAT3 pathway in vitro and in vivo. Furthermore, astrocytic gliosis and glial scar were greatly reduced in injured spinal cord treated with triptolide. Triptolide treatment was also shown to decrease the ED-1 or CD11b-positive inflammatory cells at the lesion site. Using neurofilament staining and anterograde tracing, a significantly greater number of regenerative axons were observed in the triptolide-treated rats. Importantly, behavioral tests revealed that injured rats receiving triptolide had improved functional recovery as assessed by the Basso, Beattie, and Bresnahan open-field scoring, grid-walk, and foot-print analysis. These results suggested that triptolide promoted axon regeneration and locomotor recovery by attenuating glial scaring and inflammation, and shed light on the potential therapeutic benefit for SCI.
脊髓损伤（SCI）是一种主要的神经功能障碍，目前尚无满意的治疗方法。外伤性 SCI 直接损伤神经元的胞体和/或突起，并引发一系列内源性过程，包括神经炎症反应和反应性星形胶质细胞增生。在这项研究中，我们发现雷公藤红素，一种传统中药雷公藤的主要活性成分之一，可抑制星形胶质细胞增生和炎症，并促进脊髓修复。雷公藤红素通过阻断体外和体内的 JAK2/STAT3 通路来防止星形胶质细胞的反应性激活。此外，雷公藤红素处理可大大减少损伤脊髓中的星形胶质细胞增生和胶质瘢痕。雷公藤红素治疗还可减少损伤部位 ED-1 或 CD11b 阳性炎症细胞。通过神经丝染色和顺行追踪，在雷公藤红素处理的大鼠中观察到再生轴突的数量明显增加。重要的是，行为测试显示，接受雷公藤红素治疗的损伤大鼠的功能恢复得到改善，Basso、Beattie 和 Bresnahan 旷场评分、网格行走和足迹分析评估结果。这些结果表明，雷公藤红素通过减轻胶质瘢痕和炎症来促进轴突再生和运动功能恢复，为 SCI 的潜在治疗益处提供了线索。
