姜黄素为植物姜黄的提取物，有抗炎症、抗氧化、抗凋亡和抗肿瘤等广泛的生物学作用，而姜黄素与脊髓损伤(SCI)的关系仍知之甚少。我们的预实验结果提示姜黄素通过抑制细胞凋亡促进SCI后神经功能修复，但其作用机制还有待进一步探讨。基于PI3K/AKT信号通路在细胞凋亡中起重要作用，我们提出假说：姜黄素可能通过调控PI3K/AKT通路，最终通过减轻氧化应激损伤和抗凋亡途径对SCI发挥神经保护作用。为了验证这一假说，本项目将建立脊髓损伤动物模型，采用行为学、TUNEL、Western blot和免疫组化等方法，从分子、细胞、组织以及动物整体水平等方面探讨姜黄素对SCI的神经修复作用，阐明姜黄素通过调控PI3K/AKT通路发挥神经保护作用的机制，为姜黄素治疗SCI提供理论和实验依据。

Curcumin is extracted from the tuber of Zingiberaceae plants, it have been discovered potent anti-inflammatory,anti-oxidative, anti-apoptotic and anti-tumor biological features.But the relationship between curcumin and SCI in spinal cord injury is still poorly understood.Our preliminary experimental results indicate that curcumin may play an important role in SCI, but its mechanism remains to be further explored.Therefore we put forward the hypothesis:Curcumin may play a neuroprotective role in SCI by regulating PI3K/AKT pathway, and eventually exert neuroprotective effect through attenuating oxidative stress and activating the anti-apoptotic pathway. In order to test this hypothesis, the project will set up the animal model of acute spinal cord injury，methods of behavioral, TUNEL, Western blot and immunohistochemistry were used, the important role of curcumin on SCI is discussed from the aspects of the molecular, cellular, tissue and the level of the whole animal, to clarify the mechanism of PI3K/AKT pathway on SCI of curcumin .It will lay the foundation for revealing the mechanism of SCI and provide theoretical and experimental basis for the drug treatment of SCI.

神经细胞凋亡被认为是脊髓继发性损伤加重的关键原因，抑制神经细胞继发性凋亡并逆转其功能是SCI后治疗成功的关键。姜黄素（curcumin，Cur）为植物姜黄的提取物，有着广泛的生物学作用。姜黄素可能通过减轻氧化应激损伤、抗炎和抗凋亡途径发挥保护作用。本项目将采用脊髓急性打击损伤动物模型和行为学、Western blot、TUNEL、免疫组化等实验方法，阐明姜黄素对SCI保护作用的机制，从而为姜黄素治疗SCI提供理论和实验依据。本研究采用HI-0400脊髓打击器建立大鼠急性脊髓损伤模型，姜黄素灌胃干预，BBB评分、Rivlin 斜板试验评估脊髓损伤大鼠后肢运动功能恢复，揭示姜黄素可以促进脊髓损伤后大鼠后肢运动功能恢复；SCI组炎性因子的表达在12h出现，1d增多，3d降低，而SCI+Cur组中对应的各个时间点炎性因子的的表达均降低；观察到SCI+Cur组神经细胞凋亡数量明显减少、Bax和Caspase-3的表达降低，Bcl-2的表达升高，说明姜黄素可以减少脊髓损伤后脊髓神经细胞的凋亡。检测大鼠血清中SOD活性和MDA含量的变化，实验结果表明，姜黄素可以减轻脊髓损伤后氧化应激损伤。Western blot检测结果表明，姜黄素激活PI3K/AKT通路，进而减少促凋亡蛋白Bax表达；增减Bcl-2表达；LY294002可以抑制PI3K/AKT通路，使p-AKT表达降低，Bax的表达较高，Bcl-2的表达较低。总之，本研究明确了明确姜黄素对大鼠脊髓损伤的神经保护作用，阐明姜黄素通过调控PI3K/AKT通路，最终通过减轻氧化应激损伤和抗凋亡途径对脊髓损伤发挥神经保护作用，为脊髓损伤提供新的的治疗靶点。