关键词: 沉默信息调节因子1信号, 急性颅脑损伤, 氧化应激, 炎症性应激, 细胞凋亡

Abstract: BACKGROUND: It has been shown that in a mouse model of acute traumatic brain injury, the transcriptional and translational levels of silent information regulator 1 (SIRT1) activated by drugs significantly elevates the expression of SIRT1 in brain tissue, reduces inflammatory and oxidative stress in brain tissue, and improves neurological function.
OBJECTIVE: To investigate the mechanism of intraperitoneal injection of SRT1720, an activator of SIRT1, to alleviate acute traumatic brain injury in rats. 
METHODS: Ninety Sprague-Dawley rats were randomized into three groups (n=30 per group): a sham group (without modeling), a model group and an activator group. Animal models of acute traumatic brain injury were established in the latter two groups. At 6 hours after modeling, the sham, model and activator groups were injected intraperitoneally with dimethyl sulfoxide solution, methylsulfoxide solution and SRT1720 once a day for 28 days, respectively. The time points for sampling were set, and rats’ neurological function, brain tissue water content, brain tissue oxidative stress and inflammatory response, brain tissue morphology, apoptosis and angiogenesis, and the protein expression of SIRT1 in brain tissue were detected and measured.  
RESULTS AND CONCLUSION: Compared with the sham group, the modified neurological deficit score, brain tissue water content and apoptosis rate of rats were increased in the model group at 7, 14 and 28 days of injection (P < 0.05); compared with the model group, the modified neurological deficit score, brain tissue water content and apoptosis rate of rats were decreased in the activator group (P < 0.05). Compared with the sham group, the levels of reactive oxygen radicals and myeloperoxidase in the brain tissue were increased (P < 0.05), the levels of malondialdehyde, tumor necrosis factor α and interleukin 6 in the serum were increased (P < 0.05), and the levels of superoxide dismutase in the serum were decreased in the model group at 7, 14 and 28 days of injection (P < 0.05). Compared with the model group, the levels of reactive oxygen radicals and myeloperoxidase in the brain tissue were decreased (P < 0.05), the levels of malondialdehyde, tumor necrosis factor α and interleukin 6 in the serum were decreased (P < 0.05), and the levels of superoxide dismutase in the serum were increased in the activator group at 7, 14 and 28 days of injection (P < 0.05). Immunohistochemical staining at 7, 14 and 28 days of injection showed that the number of new vessels in the brain tissue was higher in the model group than the sham group (P < 0.05) as well as higher in the activator group than the model group (P < 0.05). Western blot assay indicated that at 7, 14 and 28 days of injection, the expression of SIRT1 protein in the brain tissue was lower in the model group than the sham group (P < 0.05) and higher in the activator group than the model group (P < 0.05). Hematoxylin-eosin staining showed that at 7, 14 and 28 days of injection, the degree of brain injury in the activator group was less than that in the model group. To conclude, intraperitoneal injection of the SIRT1 signal activator SRT1720 can significantly reduce oxidative and inflammatory stress in the brain tissue, inhibit neuronal apoptosis, promote angiogenesis, and alleviate brain injury in rats with acute traumatic brain injury.

Key words: silent information regulator 1 signaling pathway, acute traumatic brain injury, oxidative stress, inflammatory stress, apoptosis