Dioscin relieves endotoxemia induced acute neuro-inflammation and protect neurogenesis via improving 5-HT metabolism.
Dioscin relieves endotoxemia induced acute neuro-inflammation and protect neurogenesis via improving 5-HT metabolism.
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薯蓣皂苷通过改善 5-HT 代谢缓解内毒素血症引起的急性神经炎症并保护神经发生
DOI：
10.1038/srep40035
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发表时间：
2017-01-06
影响因子：
4.6
通讯作者：
Yuan H
中科院分区：
文献类型：
--
作者：
Yang R;Chen W;Lu Y;Li Y;Du H;Gao S;Dong X;Yuan H
脓毒症除了导致死亡外，还是败血症幸存者认知障碍的独立危险因素。内毒素血症所致的急性神经炎症的发病机制尚不完全清楚。我们首次发现，5-羟色胺类神经递质的破坏、星形胶质细胞的神经发生和激活受损以及伴随的神经炎症是内毒素血症导致败血症幸存者急性神经炎症的潜在机制。此外，薯蓣皂苷是一种从中草药中分离出来的天然甾体皂苷，可增强5-羟色胺能系统，并通过提高海马区5-羟色胺水平而产生抗抑郁作用。海马区代谢分析也证实了这一发现，提示5-羟色胺相关代谢途径参与了内毒素血症所致急性神经炎症的发病机制。此外，通过GFAP、DCX和Ki67的定量免疫荧光分析以及实时RT-PCR分析某些基因在海马区的表达水平，对海马区的神经炎症和神经发生进行指标分析。体内和体外研究表明，薯蓣皂苷通过神经递质5-羟色胺和HMGB-1/TLR4信号通路对内毒素血症所致的海马级联性神经炎症具有保护作用，这与其在行为学测试中的治疗作用有关。因此，目前的研究结果提示薯蓣皂苷可能是治疗内毒素血症所致急性神经炎症的一种潜在方法。
Sepsis, in addition to causing fatality, is an independent risk factor for cognitive impairment among sepsis survivors. The pathologic mechanism of endotoxemia induced acute neuro-inflammation still has not been fully understood. For the first time, we found the disruption of neurotransmitters 5-HT, impaired neurogenesis and activation of astrocytes coupled with concomitant neuro-inflammation were the potential pathogenesis of endotoxemia induced acute neuro-inflammation in sepsis survivors. In addition, dioscin a natural steroidal saponin isolated from Chinese medicinal herbs, enhanced the serotonergic system and produced anti-depressant effect by enhancing 5-HT levels in hippocampus. What is more, this finding was verified by metabolic analyses of hippocampus, indicating 5-HT related metabolic pathway was involved in the pathogenesis of endotoxemia induced acute neuro-inflammation. Moreover, neuro-inflammation and neurogenesis within hippocampus were indexed using quantitative immunofluorescence analysis of GFAP DCX and Ki67, as well as real-time RT-PCR analysis of some gene expression levels in hippocampus. Ourin vivo and in vitro studiesshow dioscin protects hippocampus from endotoxemia induced cascade neuro-inflammation through neurotransmitter 5-HT and HMGB-1/TLR4 signaling pathway, which accounts for the dioscin therapeutic effect in behavioral tests. Therefore, the current findings suggest that dioscin could be a potential approach for the therapy of endotoxemia induced acute neuro-inflammation.
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