Department of Spine Surgery, Beijing Jishuitan Hospital, No 31, Xinjiekou East Street, Xicheng District, Beijing, People's Republic of China.
Neurochem Res. 2013 Apr;38(4):772-9. doi: 10.1007/s11064-013-0976-5. Epub 2013 Jan 24.
This study aimed to investigate the therapeutic effects of epigallocatechin-3-gallate (EGCG) administered by subarachnoid injection following spinal cord injury (SCI) in rats and to explore the underlying mechanism. Sprague-Dawley rats were randomly divided into four groups of 12 as follows: a sham group (laminectomy only); a control group; a 10 mg/kg EGCG-treated group; and a 20 mg/kg EGCG-treated group. SCI was induced in the rats using the modified weight-drop method (10 g × 4 cm) at the T10 (10th thoracic vertebral) level. EGCG (10 or 20 mg/kg) or vehicle as control was administered by subarachnoid injection at lumbar level 4 immediately after SCI. Locomotor functional recovery was assessed during the four weeks post-operation using open-field locomotor tests and inclined-plane tests. At the end of the study, the segments of spinal cord encompassing the injury site were removed for histopathological analysis. Immunohistochemical and Western blot analyses were performed to observe the expression of: the B cell CLL/lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). The results showed that the EGCG-treated animals had significantly better recovery of locomotor function, less myelin loss, greater Bcl-2 expression and attenuated Bax expression. In addition, the EGCG treatment significantly increased the expression of BDNF and GDNF after SCI. These findings suggest that EGCG treatment can significantly improve locomotor recovery, and this neuroprotective effect may be related to the up-regulation of BDNF and GDNF, and the inhibition of apoptosis-related proteins. Therefore, EGCG may be a promising therapeutic agent for SCI.
本研究旨在探讨腹腔注射表没食子儿茶素没食子酸酯（EGCG）对大鼠脊髓损伤（SCI）的治疗作用，并探讨其潜在机制。将 Sprague-Dawley 大鼠随机分为 4 组，每组 12 只：假手术组（仅椎板切除术）；对照组；10mg/kg EGCG 治疗组；和 20mg/kg EGCG 治疗组。采用改良的重物坠落法（10g×4cm）在 T10（第 10 胸椎）水平诱导大鼠 SCI。SCI 后立即在腰椎 4 水平通过蛛网膜下腔注射 EGCG（10 或 20mg/kg）或对照药物。术后 4 周通过旷场运动试验和斜板试验评估运动功能恢复情况。研究结束时，取出损伤部位的脊髓段进行组织病理学分析。通过免疫组织化学和 Western blot 分析观察 B 细胞 CLL/淋巴瘤-2（Bcl-2）、Bcl-2 相关 X 蛋白（Bax）、脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF）的表达。结果显示，EGCG 治疗组运动功能恢复明显更好，髓鞘丢失减少，Bcl-2 表达增加，Bax 表达减弱。此外，EGCG 治疗后 SCI 后 BDNF 和 GDNF 的表达显著增加。这些发现表明，EGCG 治疗可显著改善运动功能恢复，这种神经保护作用可能与 BDNF 和 GDNF 的上调以及凋亡相关蛋白的抑制有关。因此，EGCG 可能是 SCI 的一种有前途的治疗药物。
