rno-miR-161靶向EGLN2抑制血管性痴呆大鼠额叶铁死亡  

rno-miR-161 inhibits ferroptosis by targeting EGLN2 in VD rat model frontal lobe

作　　者：周贤熙 周丽亭 马春媚[3] 孔洁琛 苏俊芳[1] 邓汝东[1] 刘爱军[1] 陈东风[3] Zhou Xianxi;Zhou Liting;Ma Chunmei;Kong Jiechen;Su Junfang;Deng Rudong;Liu Aijun;Chen Dongfeng(Experimental Teaching Center,School of Basic Medical Sciences,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;The Affiliated Zhanjiang First Hospital of Traditional Chinese Medicine,Guangzhou University of Chinese Medicine,Zhanjiang 524000,Guangdong Province,China;Department of Human Anatomy,School of Basic Medical Sciences,Guangzhou University of Chinese Medicine,Guangzhou 510006,China)

机构地区：[1]广州中医药大学基础医学院实验教学中心,广州510006 [2]广州中医药大学附属湛江市第一中医医院,广东湛江524000 [3]广州中医药大学基础医学院人体解剖系,广州510006

出　　处：《中国临床解剖学杂志》2022年第6期665-670,共6页Chinese Journal of Clinical Anatomy

基　　金：国家自然科学基金(81673770,82174368)。

摘　　要：目的探讨rno-miR-161调控egl-9家族缺氧诱导因子2(EGLN2)对血管性痴呆(vascular dementia,VD)大鼠额叶铁死亡的影响。方法24只雄性SD大鼠按随机原则分为模型组和假手术组,模型组结扎双侧颈总动脉,假手术组不结扎双侧颈总动脉。术后4周水迷宫检测行为学。RT-qPCR检测VD模型大鼠额叶rno-miR-161的变化,RT-qPCR和Western blotting检测EGLN2和谷胱甘肽过氧化物酶4(GPX4)的表达。生物信息学预测及双荧光素酶报告基因验证rno-miR-161与EGLN2是否存在靶向调控关系。RT-qPCR及Western blotting检测rno-miR-161-mimic和rno-miR-161-inhibitor对EGLN2表达的影响。siEGLN2转染PC12细胞,检测GPX4的表达。结果与假手术组相比,模型组大鼠额叶rno-miR-161表达下降、EGLN2表达上升、GPX4表达下降。rno-miR-161直接靶向EGLN2。rno-miR-161-mimic抑制EGLN2的表达,rno-miR-161inhibitor导致EGLN2表达升高。siEGLN2促进GPX4表达。结论VD大鼠额叶中rno-miR-161靶向EGLN2抑制铁死亡。Objective To explore the effect of rno-miR-161 on regulating egl-9 hypoxia-inducible factor 2(EGLN2)in frontal ferroptosis in vascular dementia(VD)rat.Methods Twenty-four adult male SD rats were randomly divided into a control group(sham),a model group(VD).The VD group was obtained by bilateral carotid artery ligation,while the sham group was not ligated with bilateral carotid artery.The Morris water maze test was applied to assess the symptoms of VD 4 weeks after surgery.RT-qPCR was used to detect the changes of rno-miR-161.RT-qPCR and Western blotting were used to detect the expression levels of EGLN2 and glutathione-dependent antioxidant enzyme glutathione peroxidase 4(GPX4).The relationship between rno-miR-161 and EGLN2 was predicted by bioinformatics and luciferase reporter gene test.RT-qPCR and Western blotting were used to detect the effect of rno-miR-161-mimic and rno-miR-161-inhibitor on EGLN2 expression.The expression of EGLN2 was interfered by interference technology and the expression of GPX4 was detected by Western blotting and RT-qPCR.Results Compared with the control group,the expression of rno-miR-161 was down-regulated in the frontal lobe,the EGLN2 expression was increased while GPX4 was down-regulated.The EGLN2 was the direct target of rno-miR-161.rno-miR-161-minic inhibited the expression of EGLN2,rno-miR-161-inhibitor resulted in higher EGLN2 expression.siEGLN2 promoted GPX4.Conclusions rno-miR-161 inhibits ferroptosis by targeting EGLN2 expression in VD rat model frontal lobe.

关 键 词：血管性痴呆 rno-miR-161 EGLN2 铁死亡 GPX4 

分 类 号：R361.3[医药卫生—病理学] R743.9[医药卫生—基础医学]