Metformin Protects Against Spinal Cord Injury by Regulating Autophagy via the mTOR Signaling Pathway
Metformin Protects Against Spinal Cord Injury by Regulating Autophagy via the mTOR Signaling Pathway
复制标题
双过氧钒通过激活 erK1/2 信号传导调节自噬，从而防止脊髓损伤
DOI：
10.1007/s11064-018-2525-8
复制
发表时间：
2018-05-01
影响因子：
4.4
通讯作者：
He, Xijing
中科院分区：
文献类型：
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作者：
Guo, Yue;Wang, Fang;He, Xijing
脊髓损伤（SCI）是一种严重的中枢性创伤，可导致严重的运动和感觉系统功能障碍。继发性损伤，如细胞凋亡和细胞自噬，显着影响运动功能的恢复过程。二甲双胍是目前世界上广泛使用的2型糖尿病口服降糖药。它已被证明在神经系统中促进自噬和抑制细胞凋亡。然而，其在SCI后恢复中的作用仍然未知。在本研究中，我们确定了使用Basso、Beattie和Bresnahan（BBB）运动评估量表评估的运动功能在损伤后接受二甲双胍治疗的大鼠中显著更高。尼氏染色显示二甲双胍也增加了脊髓损伤中存活神经元的数量。Western blot和免疫荧光分析显示，脊髓损伤后二甲双胍治疗的动物中，哺乳动物雷帕霉素靶蛋白（mTOR）和P70 S6激酶（P70 S6 K）减少，而自噬标记物的表达增加，凋亡标记物减少。综上所述，这些发现表明二甲双胍通过调节mTOR/P70 S6 K信号通路促进自噬和抑制凋亡，在SCI后发挥神经保护剂的作用。
Spinal cord injury (SCI) is a serious central trauma, leading to severe dysfunction of motor and sensory systems. Secondary injuries, such as apoptosis and cell autophagy, significantly impact the motor function recovery process. Metformin is a widely used oral anti-diabetic agent for type 2 diabetes in the world. It has been demonstrated to promote autophagy and inhibit apoptosis in the nervous system. However, its role in recovery following SCI is still unknown. In this study, we determined that motor function, assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor assessment scale, was significantly higher in rats treated with metformin following injury. Nissl staining revealed that metformin also increased the number of surviving neurons in the spinal cord lesion. Western blot and immunofluorescent analysis revealed that mammalian target of rapamycin (mTOR) and P70S6 kinase (P70S6K) decreased, while the expression of autophagy markers increased and apoptosis markers declined in animals treated with metformin following SCI. Taken together, these findings suggest that metformin functions as a neuroprotective agent following SCI by promoting autophagy and inhibiting apoptosis by regulating the mTOR/P70S6K signaling pathway.