Protective Effects of SIRT6 Against Inflammation, Oxidative Stress, and Cell Apoptosis in Spinal Cord Injury
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ORIGINAL ARTICLE
Protective Effects of SIRT6 Against Inflammation, Oxidative Stress, and Cell Apoptosis in Spinal Cord Injury Chen Zhaohui1 and Wu Shuihua
1,2
Accumulating evidence supports that Sirtuin 6 (SIRT6) may play a vital role in the pathogenesis of spinal cord injury. The current study was designed to investigate the specific effects of SIRT6 on spinal cord injury (SCI). HE and Nissl staining were performed for pathological analysis in SCI rats. SIRT6 expression was detected by RT-qPCR. CCK8 assay was applied for the detection of cell viability of LPS-injured PC12 cells. TNF-a, IL-1β, IL-6, MCP-1 levels and ROS, MPO, SOD levels were assessed to evaluate inflammation and oxidative stress in spinal cord injury. Cell apoptosis were evaluated by morphological examination using AO/EB fluorescent staining methods and key proteins related to apoptosis were explored via western blot. HE staining revealed increased cavity involving the dorsal white matter and central gray matter, and Nissl staining discovered the loss of motor neurons in the ventral horn in SCI rats. SIRT6 had lower expression in SCI rats. Lipopolysaccharide (LPS) exposure induced cell apoptosis and reduced the expression of SIRT6. Mechanistically, we revealed that up-regulation of SIRT6 alleviated inflammation and oxidative stress and inhibited cell apoptosis in spinal cord injury. Together, our findings indicated that SIRT6 attenuated spinal cord injury by suppressing inflammation, oxidative stress, and cell apoptosis. This study demonstrates that SIRT6 may represent a protective effect against spinal cord injury.
Abstract—
KEY WORDS: SIRT6; inflammation; oxidative stress; apoptosis; spinal cord injury.
INTRODUCTION Spinal cord injury (SCI) is a serious disabling disease caused by a series of internal and external factors in orthopedics and neuroscience [1]. It usually results in loss of movement, sensation, and excretory 1
Department of Neurosurgery, Hunan Children’s Hospital, No. 86 Ziyuan Road, Yuhua District, Changsha City, 410000, Hunan Province, China 2 To whom correspondence should be addressed at Department of Neurosurgery, Hunan Children’s Hospital, No. 86 Ziyuan Road, Yuhua District, Changsha City, 410000, Hunan Province, China. E-mail: [email protected]
function below the injured segment of patients [2]. SCI not only brings unimaginable psychological distress and life obstacles to the patients but also causes high burden to the families and the community [3]. Thus, the treatment of SCI has been the research priorities in basic medicine and clinical medicine in recent years. The pathological process of SCI starts with the primary injury process directly caused by a mechanical force and follows the secondary injury process caused by microcirculation disorders and inflammatory responses [4, 5]. Primary injuries of the spinal cord are irreversible in the
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Zhaohui, and Shuihua pathophysiological process [6]. Hence, most studies focus on prev
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