敲除趋化性细胞因子受体5降低小鼠脑出血后细胞铁死亡  

Knockout of CCR5 alleviates ferroptosis after intracerebral hemorrhage in mice

作　　者：曲洪玮 卢凯 黄珊珊[1] 朱遂强[1] Qu Hongwei;Lu Kai;Huang Shanshan;Zhu Suiqiang(Department of Neurology,Tongji Hospital,Tongji Medical college,Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院神经内科,武汉430030

出　　处：《中国组织化学与细胞化学杂志》2022年第2期152-157,共6页Chinese Journal of Histochemistry and Cytochemistry

基　　金：湖北省自然科学基金面上项目(2020CFB805);2019湖北省技术创新专项(重大项目)(2019ACA132)。

摘　　要：目的检测敲除趋化性细胞因子受体5(C-C chemokine receptor 5,CCR5)基因对小鼠脑出血模型细胞铁死亡的影响,以明确CCR5在脑出血时损伤时细胞铁死亡中的作用。方法选取CCR5基因敲除小鼠及野生型(WT)小鼠各6只随机分成4组构建ICH模型和对照模型,于造模后72 h取脑组织,应用免疫组织化学染色及免疫印迹分析检测铁死亡标记物谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)的表达。结果WT小鼠脑出血后,脑组织中GPX4阳性神经元数和GPX4免疫反应性较无脑出血WT小鼠脑组织中GPX4阳性神经元和GPX4免疫反应性明显降低;CCR5基因敲除小鼠脑出血后,脑组织中GPX4阳性神经元和GPX4免疫反应性虽较无脑出血CCR5基因敲除小鼠脑组织中GPX4阳性神经元和GPX4免疫反应性降低,但明显高于脑出血WT小鼠脑组织中GPX4阳性神经元和GPX4免疫反应性。结论在脑出血小鼠模型中,敲除CCR5可以减轻脑出血后细胞铁死亡,提示CCR5参与脑出血时损伤时细胞铁死亡。Objective To detect the effect of C-C chemokine receptor 5(CCR5)gene knockout on cell ferroptosis in the mouse intracerebral hemorrhage model,so as to clarify the role of CCR5 in the cell ferroptosis during cerebral hemorrhage injury.Methods Six CCR5 gene knockout mice and six wild-type(WT)mice were selected and randomly divided into four groups to construct intracerebral hemorrhage model and the control.The peri-surgerical brain tissues were taken 72 hours after modeling.The expression of glutathione peroxidase 4(GPx4),a ferroptosis marker,was detected by immunohistochemical staining and Western blot analysis.Results After intracerebral hemorrhage in WT mice,the number of GP X4 positive neurons and GPX4 immunoreactivity in brain tissue were significantly lower than those in WT mice without intracerebral hemorrhage;after intracerebral hemorrhage in CCR5 knockout mice,the number of GPX4 positive neurons and GPX4 immunoreactivity in brain tissue were lower than those in CCR5 knockout mice without intracerebral hemorrhage,but significantly higher than those WT mice with intracerebral hemorrhage.Conclusion In a mouse model of intracerebral hemorrhage,CCR5 knockout could alleviate ferroptosis caused by intracerebral hemorrhage,suggesting that CCR5 is involved in the cell ferroptosis during intracerebral hemorrhage injury.

关 键 词：脑出血 趋化性细胞因子受体5 铁死亡 谷胱甘肽过氧化物酶4 

分 类 号：R365[医药卫生—病理学] R741.02[医药卫生—基础医学]