Akebia Saponin D prevents axonal loss against TNF-induced optic nerve damage with autophagy modulation.

Akebia Saponin D prevents axonal loss against TNF-induced optic nerve damage with autophagy modulation.
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DOI:
10.1007/s11033-020-06008-y
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发表时间:
2020-12
影响因子:
2.8
通讯作者:
Kitaoka Y
Kitaoka Y
中科院分区:
生物学4区
文献类型:
--
作者:
Sase K;Tsukahara C;Fujita N;Arizono I;Takagi H;Kitaoka Y

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木犀草皂苷D (ASD)是一种三萜皂苷,对某些神经细胞具有保护作用。本研究的目的是探讨ASD预防肿瘤坏死因子(TNF)诱导的轴突损失的可能性以及ASD对视神经自噬生物学过程的调节。大鼠玻璃体内给予TNF,同时给予2,20或200 pmol ASD和TNF,或单独给予ASD。免疫印迹法检测视神经中LC3-II、自噬通量标志物p62的表达及磷酸化p38 (p-p38)的表达。形态计量学分析显示,ASD对tnf诱导的视神经损伤有显著改善作用。在接受tnf治疗的眼睛中,视神经中的p62显著增加,但ASD完全阻止了这种增加。与pbs处理的对照眼相比,ASD单独注射显示p62水平显著降低。注射了tnf的ASD治疗后,LC3-II显著升高。在接受tnf治疗的眼睛中,视神经中的p-p38显著增加,但ASD完全阻止了这种增加。ASD的保护作用可能与增强自噬激活和抑制p-p38有关。
Akebia Saponin D (ASD), a triterpenoid saponin, was shown to have protective effects in certain neuronal cells. The purpose of the present study was to investigate the possibility of ASD to prevent tumor necrosis factor (TNF)-induced axonal loss and the ASD modulation of the biologic process of autophagy in optic nerves. Rats were given intravitreal administration of TNF, simultaneous administration of 2, 20, or 200 pmol ASD and TNF, or ASD alone. LC3-II and p62 expression, which is a marker of autophagic flux, and phosphorylated p38 (p-p38) expression in optic nerves were examined by immunoblot analysis. Morphometric analysis revealed a significant ameliorated effect of ASD against TNF-induced optic nerve damage. p62 was significantly increased in the optic nerve in TNF-treated eyes, but this increase was totally prevented by ASD. The ASD alone injection showed significant reduction of p62 levels compared with the PBS-treated control eyes. LC3-II was significantly increased by ASD treatment in the TNF-injected eyes. p-p38 was significantly increased in the optic nerve in TNF-treated eyes, but this increase was completely prevented by ASD. The protective effects of ASD may be associated with enhanced autophagy activation and inhibition of p-p38.
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