香芹酚通过减轻铁死亡缓解缺血/再灌注诱导的海马神经元损伤的神经保护作用。
The neuroprotective effects of carvacrol on ischemia/reperfusion-induced hippocampal neuronal impairment by ferroptosis mitigation.
机构信息
Department of Pharmacology, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319, China.
Department of Scientific Research, Third Affiliated Hospital of Gui zhou Medical University, Du yun, Gui zhou, 558000, China.
出版信息
Life Sci. 2019 Oct 15;235:116795. doi: 10.1016/j.lfs.2019.116795. Epub 2019 Aug 27.
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 biomarkers; 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.
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的功能和数量减少。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，特别是铁水平对神经元损伤的调节作用，从未得到系统研究。本研究旨在揭示香芹酚在沙土鼠缺血性中风后保护海马神经元损伤的机制。
材料和方法
通过 Morris 水迷宫试验评估学习和记忆障碍。通过试剂盒检测铁离子含量和氧化应激指数。通过 MTT 测定法评估细胞活力。通过电子显微镜和 Western blot 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。Morris 水迷宫试验表明，香芹酚处理的沙土鼠的学习和记忆能力显著提高。通过测量脂质过氧化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性沙土鼠脑组织中脂质过氧化水平。进行组织病理学检查和 Western blot 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细胞死亡形式的蛋白质水平来评估海马体中的铁死亡。这些结果表明，香芹酚通过增加谷胱甘肽过氧化物酶 4（GPx4）的表达来减少细胞死亡，从而抑制铁死亡。本研究表明，香芹酚可能是治疗脑缺血的一种有价值的药物。
结论
香芹酚通过增加 GPx4 的表达抑制铁死亡，为沙土鼠的海马神经元提供对 I/R 的保护。
Zotero 插件