Diosgenin Glucoside Protects against Spinal Cord Injury by Regulating Autophagy and Alleviating Apoptosis.

Diosgenin Glucoside Protects against Spinal Cord Injury by Regulating Autophagy and Alleviating Apoptosis.
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薯蓣皂苷元葡萄糖苷通过调节自噬和减轻细胞凋亡来预防脊髓损伤

DOI:
10.3390/ijms19082274
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发表时间:
2018-08-02
影响因子:
5.6
通讯作者:
Huang FJ
Huang FJ
中科院分区:
生物学2区
文献类型:
--
作者:
Chen XB;Wang ZL;Yang QY;Zhao FY;Qin XL;Tang XE;Du JL;Chen ZH;Zhang K;Huang FJ

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脊髓损伤(SCI)是一种严重的创伤性中枢神经系统(CNS)损伤,只有有限的恢复治疗选择。薯蓣皂苷元葡萄糖苷(Diosgenin glucoside,DG)是延龄草(Trillium tschonoskii Max.)通过其抗氧化和抗凋亡功能具有神经保护作用。在这项研究中,我们研究了DG治疗SCI的治疗益处和潜在机制。我们发现,在创伤性SCI的Sprague-Dawley大鼠中,自噬标志物轻链3(LC 3)和Beclin 1的表达降低,同时自噬底物蛋白p62和泛素化蛋白的积累,表明自噬活性受损。然而,DG处理由于miR-155- 3 p的下调而显著减弱了p62表达并上调了Rheb/mTOR信号传导途径(证明为在脑中富集的Ras同源物)。我们还观察到DG治疗组的组织损伤和水肿明显减少,与对照组相比,功能恢复明显。总的来说,DG治疗所提供的神经保护作用值得进一步研究其在SCI中的治疗潜力。
Spinal cord injury (SCI) is a severe traumatic lesion of central nervous system (CNS) with only a limited number of restorative therapeutic options. Diosgenin glucoside (DG), a major bioactive ingredient of Trillium tschonoskii Max., possesses neuroprotective effects through its antioxidant and anti-apoptotic functions. In this study, we investigated the therapeutic benefit and underlying mechanisms of DG treatment in SCI. We found that in Sprague-Dawley rats with traumatic SCI, the expressions of autophagy marker Light Chain 3 (LC3) and Beclin1 were decreased with concomitant accumulation of autophagy substrate protein p62 and ubiquitinated proteins, indicating an impaired autophagic activity. DG treatment, however, significantly attenuated p62 expression and upregulated the Rheb/mTOR signaling pathway (evidenced as Ras homolog enriched in brain) due to the downregulation of miR-155-3p. We also observed significantly less tissue injury and edema in the DG-treated group, leading to appreciable functional recovery compared to that of the control group. Overall, the observed neuroprotection afforded by DG treatment warrants further investigation on its therapeutic potential in SCI.
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