Nicotinamide Adenine Dinucleotide Protects against Spinal Cord Ischemia Reperfusion Injury-Induced Apoptosis by Blocking Autophagy

作者：Xie, Lei; Yu, Sifei; Wang, Zhenfei; Yang, Kai; Liu, Zhuochao; Li, Changwei^*; Liang, Yu^*

来源：Oxidative Medicine and Cellular Longevity, 2017, 2017: 7063874.

DOI：10.1155/2017/7063874

• ISCHEMIA/REPERFUSION INJURY
• THERAPEUTIC TARGETS
• NAD(+) METABOLISM
• ANEURYSM REPAIR
• AORTIC-SURGERY
• BRAIN-INJURY
• CELL-DEATH
• ACTIVATION
• INHIBITION
• RECOVERY

The role of autophagy, neuroprotective mechanisms of nicotinamide adenine dinucleotide (NAD(+)), and their relationship in spinal cord ischemic reperfusion injury (SCIR) was assessed. Forty-eight Sprague-Dawley rats were divided into four groups: sham, ischemia reperfusion (I/R), 10 mg/kg NAD(+), and 75 mg/kg NAD(+). Western blotting, immunofluorescence, and immunohistochemistry were used to assess autophagy and apoptosis. Basso, Beattie, and Bresnahan (BBB) scores were used to assess neurological function. Expression levels of Beclin-1, Atg12-Atg5, LC3B-II, cleaved caspase 3, and Bax were upregulated in the I/R group and downregulated in the 75 mg/kg NAD(+) group; p-mTOR, p-AKT, p62, and Bcl-2 were downregulated in the I/R group and upregulated in the 75 mg/kg NAD(+) group. Numbers of LC3B-positive, caspase 3-positive, Bax-positive, and TUNEL-positive cells were significantly increased in the I/R group and decreased in the 75 mg/kg NAD(+) group. The mean integrated option density of Bax increased and that of Nissl decreased in the I/R group, and it decreased and increased, respectively, in the 75 mg/kg NAD(+) group. BBB scores significantly increased in the 75 mg/kg NAD(+) group relative to the I/R group. No difference was observed between I/R and 10 mg/kg NAD(+) groups for these indicators. Therefore, excessive and sustained autophagy aggravates SCIR; administration of NAD(+) alleviates injury.

• 出版日期2017
• 单位上海市闵行区中心医院; 上海交通大学