MP Resulting in Autophagic Cell Death of Microglia through Zinc Changes against Spinal Cord Injury.
MP Resulting in Autophagic Cell Death of Microglia through Zinc Changes against Spinal Cord Injury.
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MP 通过锌变化导致小胶质细胞自噬细胞死亡以对抗脊髓损伤
DOI：
10.1155/2016/6090316
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发表时间：
2016
影响因子：
--
通讯作者：
Mei X
中科院分区：
文献类型：
--
作者：
Li D;Wang G;Han D;Bi J;Li C;Wang H;Liu Z;Gao W;Gao K;Yao T;Wan Z;Li H;Mei X
甲基强的松龙脉冲治疗（MPPT）作为一种公认的脊髓损伤治疗方法，近年来受到质疑，其治疗脊髓损伤的确切机制尚不清楚。本研究旨在探讨MP对脊髓损伤的确切影响。我们在体内和体外LPS诱导的脊髓损伤模型中检测了MP的作用。我们发现，给药MP使受伤大鼠的Basso、Beattie和Bresnahan评分和运动神经元计数增加。此外，MP在体内活化的小胶质细胞数量明显减少，在LPS诱导的模型中，MP可诱导Beclin-1依赖性小胶质细胞自噬死亡。同时，MP可提高细胞锌浓度和ZIP8水平，TPEN可逆转MP对小胶质细胞自噬死亡的影响。最后，我们发现MP在LPS诱导的模型中具有抑制NF-κβ的作用。这些结果表明，MP可导致小胶质细胞自噬死亡，其主要依赖于增加细胞不稳定锌，并可能与抑制NF-κβ有关，MP可在脊髓损伤中产生神经保护作用。
Methylprednisolone pulse therapy (MPPT), as a public recognized therapy of spinal cord injury (SCI), is doubted recently, and the exact mechanism of MP on SCI is unclear. This study sought to investigate the exact effect of MP on SCI. We examined the effect of MP in a model of SCI in vivo and an LPS induced model in vitro. We found that administration of MP produced an increase in the Basso, Beattie, and Bresnahan scores and motor neurons counts of injured rats. Besides the number of activated microglia was apparently reduced by MP in vivo, and Beclin-1 dependent autophagic cell death of microglia was induced by MP in LPS induced model. At the same time, MP increases cellular zinc concentration and level of ZIP8, and TPEN could revert effect of MP on autophagic cell death of microglia. Finally, we have found that MP could inhibit NF-κβ in LPS induced model. These results show that the MP could result in autophagic cell death of microglia, which mainly depends on increasing cellular labile zinc, and may be associated with inhibition of NF-κβ, and that MP can produce neuroprotective effect in SCI.