褪黑素通过AKT/Nrf2通路抑制氧化应激减轻脑外伤小鼠脑水肿

Melatonin inhibits oxidative stress through AKT-Nrf2 pathway to reduce brain edema in mice with traumatic brain injury

目的本研究旨在探讨褪黑素(Mel)对脑外伤模型小鼠的作用及其潜在机制。方法选用6~8周龄雄性C57BL/6小鼠构建脑外伤模型,造模后1 h及之后连续3d以10 mg/kg Mel进行腹腔注射。对各组小鼠进行神经功能缺损评分(NSS),计算脑组织水含量。测定丙二醛(MDA)与超氧化物歧化酶(SOD)水平用于评估氧化应激水平。TUNEL与Nissl染色检测细胞凋亡和损伤情况。Western blot法检测凋亡相关蛋白以及AKT/Nrf2信号通路相关蛋白的表达情况。结果Mel显著改善神经功能障碍,减轻脑水肿。Mel降低MDA、增加SOD水平抑制氧化应激。Mel降低c-Caspase-3和Bax表达,上调Bcl-2表达,减少神经细胞凋亡和神经元的损伤。Mel激活AKT/Nrf2通路,上调HO-1和NQO-1的表达。结论Mel通过激活AKT/Nrf2通路抑制氧化应激减轻脑外伤小鼠脑水肿。

Objective To investigate the function of melatonin(Mel)on traumatic brain injury(TBI)model and its potential mechanisms.Methods TBI was induced in C57BL/6 mice 6~8 weeks old.The mice were treated with Mel intraperitoneally at 30 minutes after TBI and 1 and 3 days post-TBI.The modified neurological severity score(NSS)tests were performed.The brain edema was analyzed by dry–wet weight method.The levels of malonaldehyde(MDA)and superoxide dismutase(SOD)were determined.Damage and apoptosis of cells was measured by Nissl and TUNEL staining.The expression of apoptotic proteins and AKT/Nrf2 signaling pathway-related proteins were measured by western blot.Results Mel significantly improved neurological dysfunction and reduced cerebral edema.Mel reduces MDA,increases SOD and inhibits oxidative stress.Mel decreased the expression of c-Caspase-3 and Bax,upregulated the expression of Bcl-2,and reduced the apoptosis of nerve cells and the damage of neurons.Mel activated AKT/Nrf2 pathway and upregulated the expression of HO-1 and NQO-1.Conclusion Mel inhibits oxidative stress by activating AKT/Nrf2 pathway to reduce cerebral edema in rats with traumatic brain injury.