Metformin preconditioning provide neuroprotection through enhancement of autophagy and suppression of inflammation and apoptosis after spinal cord injury
Metformin preconditioning provide neuroprotection through enhancement of autophagy and suppression of inflammation and apoptosis after spinal cord injury
复制标题
二甲双胍预处理通过增强自噬并抑制脊髓损伤后的炎症和细胞凋亡来提供神经保护
DOI：
10.1016/j.bbrc.2016.05.148
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发表时间：
2016-09-02
影响因子：
3.1
通讯作者：
Mei, Xifan
中科院分区：
文献类型：
--
作者：
Wang, Chen;Liu, Chang;Mei, Xifan
脊髓损伤（Spinal cord injury，SCI）是最严重的神经系统疾病之一，其特点是发病率高，致残率高。炎症反应和自噬反应在SCI的发生发展中起着重要作用。二甲双胍是治疗2型糖尿病的一线药物，具有促进神经系统自噬以及抗炎和抗凋亡的特性。本研究探讨二甲双胍预处理对大鼠脊髓损伤后神经保护作用。Basso、Beattie和Bresnahan评分、HE染色和Nissl染色结果显示二甲双胍对脊髓损伤后运动神经元的功能和数量有保护作用。Western blot结果显示，二甲双胍可增强脊髓损伤后Beclin-1和LOB-II的表达，降低mTOR和p70 S6 K的磷酸化水平。二甲双胍显著降低NF-κ B的表达。此外，Western blot和免疫荧光结果表明，二甲双胍降低了caspase 3的激活，而bcl-2水平显着增加。因此，二甲双胍通过抑制细胞凋亡和炎症并通过mTOR/p7 OS 6 K信号通路增强自噬来减轻SCI。(C)2016 Elsevier Inc. All rights reserved.
Spinal cord injury (SCI) is one of the most serious nervous system disorders characterised by high morbidity and disability. Inflammatory and autophagy responses play an important role in the development of SCI. Metformin, a first-line drug for type-2 diabetes, features autophagy promotion as well as anti-inflammatory and anti-apoptotic properties in the nervous system. In this study, we investigated the neuroprotection effects of metformin preconditioning on rats after SCI. Results of Basso, Beattie and Bresnahan scores, HE staining and Nissl staining showed that the function and quantity of motor neurons were protected by metformin after SCI. Western blot revealed that the expression of Beclin-1 and LOB-II was enhanced, and the phosphorylation levels of the mammalian target of rapamycin (mTOR) protein and p70S6K were reduced by metformin after SCI. Metformin significantly reduced the expression of NF KB. Moreover, Western blot and immunofluorescence results indicated that caspase 3 activation was reduced, whereas bcl-2 level was significantly increased by metformin. Hence, metformin attenuated SCI by inhibiting apoptosis and inflammation and enhancing the autophagy via the mTOR/p7OS6K signalling pathway. (C) 2016 Elsevier Inc. All rights reserved.