The neuroprotective effects of carvacrol on ischemia/reperfusion-induced hippocampal neuronal impairment by ferroptosis mitigation
The neuroprotective effects of carvacrol on ischemia/reperfusion-induced hippocampal neuronal impairment by ferroptosis mitigation
复制标题
香芹酚通过缓解铁死亡对缺血/再灌注引起的海马神经元损伤的神经保护作用
DOI：
10.1016/j.lfs.2019.116795
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发表时间：
2019-10-15
期刊：
影响因子：
6.1
通讯作者：
Wang, Peng
中科院分区：
文献类型：
--
作者：
Guan, Xueying;Li, Xiaolei;Wang, Peng
目的：脑缺血是最常见的神经元损伤类型，其特征是海马神经元功能和数量减少。香芹酚在脑缺血中具有显著的神经保护作用。然而，香芹酚影响脑缺血的机制，特别是在铁水平对神经元损伤的调节方面，从未得到系统研究。本研究旨在揭示香芹酚对沙鼠缺血性脑卒中后海马神经元损伤的保护机制。
材料和方法：采用莫里斯水迷宫试验评估学习和记忆障碍。用试剂盒检测铁离子含量和氧化应激指标。采用MTT法评估细胞活力。通过电子显微镜照片和蛋白质印迹法检测形态和分子特征。
结果：在本研究中，我们证明了香芹酚在体内和体外的神经保护作用。莫里斯水迷宫试验表明，香芹酚处理的沙鼠学习和记忆能力显著提高。通过测量脂质过氧化物生物标志物的水平来评估脂质过氧化损伤；结果表明香芹酚降低了缺血沙鼠脑组织中脂质过氧化物的水平。进行组织病理学检查和蛋白质印迹分析以评估神经元损伤，香芹酚减少了细胞死亡。此外，通过测量参与这种铁依赖性调节性细胞死亡形式的蛋白质水平来评估海马中的铁死亡。这些结果表明香芹酚减少了细胞死亡，并且香芹酚通过增加谷胱甘肽过氧化物酶4（GPx4）的表达抑制铁死亡。本研究表明香芹酚可能是一种治疗脑缺血的有价值的药物。
结论：香芹酚通过增加GPx4的表达抑制铁死亡，从而为沙鼠海马神经元抵抗缺血/再灌注提供保护。
Objective: Cerebral ischemia is the most common type of neuronal injury and is characterized by a reduction in the function and number of hippocampal neurons. Carvacrol has a significant neuroprotective effect in cerebral ischemia. However, the mechanisms by which carvacrol affects cerebral ischemia, especially with respect to the regulation of neuronal damage by iron levels, have never been systematically studied. This study aimed to reveal the mechanisms by which carvacrol protects against hippocampal neuron impairment after ischemic stroke in gerbils.Materials and methods: The Morris water maze test was performed to evaluate learning and memory impairments. Iron ion content and oxidative stress index were detected by the kit. MTT assay was performed to assess the cell viability. The morphology and molecular characteristics were detected by electron micrographs and western blot.Results: In the present study, we demonstrated the neuroprotective effects of carvacrol in vivo and in vitro. The Morris water maze test showed that the learning and memory abilities of the gerbils treated with carvacrol were significantly improved. Lipid peroxide injury was evaluated by measuring the levels of lipid peroxide bio-markers; the results indicated that carvacrol decreased the level of lipid peroxide in ischemic gerbil brain tissue. Histopathological examinations and western blotting were performed to evaluate injury in neurons, and carvacrol reduced cell death. Moreover, ferroptosis in the hippocampus was evaluated by measuring the levels of proteins involved in this iron-dependent form of regulated cell death. These results indicated that carvacrol reduced cell death and that carvacrol inhibited ferroptosis by increasing the expression of glutathione peroxidase 4(GPx4). This study showed that carvacrol may be a valuable drug for treating cerebral ischemia.Conclusion: Carvacrol provides protection for hippocampal neurons against I/R in gerbils by inhibiting ferroptosis through increasing the expression of GPx4.