褪黑素抑制早期蛛网膜下腔出血大鼠皮层神经细胞铁死亡  

Melatonin inhibits the ferroptosis of cerebral cortex in rats with early subarachnoid hemorrhage

作　　者：雷伟 郝广志 邹正 陈立刚 董玉书 Lei Wei;Hao Guangzhi;Zou Zheng;Chen Ligang;Dong Yushu(Institute of Neuroscience,General Hospital of Northern Theater Command Base,Shenyang 110016,China)

机构地区：[1]中国人民解放军北部战区总医院神经外科,沈阳110016

出　　处：《神经解剖学杂志》2021年第4期454-458,共5页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81671313,82071481);全军医学科技青年培育计划拔尖项目(17QNP053)。

摘　　要：目的:研究褪黑素(Mel)对蛛网膜下腔出血大鼠(SAH)早期皮层神经细胞铁死亡的影响及分子机制。方法:利用注射自体血液的方法制备SAH大鼠模型,通过腹腔注射法给予褪黑素治疗。利用商品化试剂盒检测脑脊液中铁离子含量和脑组中铁含量,利用Western Blot检测大鼠皮层中谷胱甘肽过氧化物酶4(GPX4)的表达,利用2’,7’-二氯二氢荧光素二乙酸酯(DCFH-DA)荧光探针法检测大鼠皮层组织中反应性活性氧(ROS)的含量。结果:SAH模型大鼠脑脊液和皮层组织中铁含量增加,GPX4蛋白的表达降低,而ROS含量增加。褪黑素治疗可以促进SAH大鼠皮层中GPX4表达而降低ROS含量。结论:褪黑素可以通过增加GPX4的表达减轻SAH大鼠皮层中氧化应激反应,进而减轻皮层神经细胞铁死亡。Objective: To investigate the effect of melatonin on ferroptosis of cerebral cortex in early subarachnoid hemorrhage (SAH) rats and its molecular mechanism. Methods: SAH rat model was prepared by injecting autologous blood. Melatonin was administered by intraperitoneal injection. The content of iron in cerebrospinal fluid (CSF) and brain tissues was detected by commercial kits. The expression of glutathione peroxidase 4 (GPX4) in the cortex of rats was detected by Western Blot. Reactive oxygen species (ROS) levels were analyzed to assess the level of oxidative stress using 2’,7’-dichlorofluorescin diacetate (DCFH-DA) fluorescence. Results: The content of iron in cerebrospinal fluid and cortical tissue of SAH model rats increased. The expression of GPX4 protein decreased. Meanwhile,the content of ROS increased. Melatonin treatment can promote the expression of GPX4 and reduce the ROS content in the cortex of SAH rats. Conclusion: Melatonin can reduce oxidative stress and ferroptosis of cerebral cortical nerve cells in SAH rats by increasing GPX4 expression.

关 键 词：褪黑素 铁死亡 蛛网膜下腔出血 早期脑损伤 大鼠 

分 类 号：R743.35[医药卫生—神经病学与精神病学]