神经保护
脑出血
医学
药理学
细胞凋亡
神经炎症
维尔达格利普汀
标记法
程序性细胞死亡
氧化应激
丙二醛
麻醉
内分泌学
免疫学
炎症
糖尿病
化学
2型糖尿病
生物化学
免疫组织化学
蛛网膜下腔出血
作者
Yan Zhang,Xiangyu Zhang,V. Wee Yong,Mengzhou Xue
标识
DOI:10.1016/j.neulet.2022.136579
摘要
Intracerebral hemorrhage (ICH) is a fatal health problem which lacks effective treatment. The apoptosis caused by hematoma constituents, and the ferroptosis due to iron overload, are prominent contributors of neurologic impairment after ICH. Targeting cell death pathways may thus be a therapeutic strategy for neuroprotection and functional recovery in ICH. Vildagliptin (Vilda), a dipeptidyl peptidase (DPP)-4 inhibitor, has been reported to have potent anti-apoptosis and anti-ferroptotic capacity. However, it is not clear whether Vilda has anti-cell death efficacy in ICH. In the present study, the potential neuroprotective effect of Vilda in ICH mice was investigated. Mice were randomly divided into three groups: sham, ICH + saline or ICH + Vilda. ICH was induced by collagenase type VII micro-injection into the right basal ganglia. Vilda (50 mg/kg/day; gavage) daily treatment for 3 days after ICH improved neurological deficit scores, reduced hematoma volume, and inhibited degeneration of neurons. The activation of microglia/macrophages and infiltration of neutrophil were restrained by Vilda. Moreover, Vilda attenuated brain cell apoptosis as determined by TUNEL staining, raised Bcl-2 protein level, and simultaneously suppressed Bax as validated by western blots. In addition, Vilda reduced malondialdehyde level, elevated glutathione peroxidase brain content, and alleviated iron deposition at 3 days after ICH in mice. In conclusion, Vilda exerts neuroprotective effects in ICH, at least in part by inhibiting neuroinflammation, and preventing neuronal apoptosis and ferroptosis following ICH.
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