LncRNA CRNDE Deteriorates Delayed Encephalopathy After Acute Carbon Monoxide Poisoning to Inactivate AKT/GSK3β/β-catenin Pathway via miR-212-5p
LncRNA CRNDE Deteriorates Delayed Encephalopathy After Acute Carbon Monoxide Poisoning to Inactivate AKT/GSK3β/β-catenin Pathway via miR-212-5p
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DOI：
10.1007/s12640-022-00518-2
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发表时间：
2022-07-19
影响因子：
3.7
通讯作者：
Pang，Li
中科院分区：
文献类型：
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作者：
Liu，Zuo-Long;Bian，Miao;Pang，Li
急性一氧化碳中毒后迟发性脑病（DEACMP）是急性一氧化碳中毒最严重的后遗症，伴有脑结构或功能损伤。LncRNA结直肠癌差异表达（CRNDE）异常表达参与神经细胞损伤；然而，CRNDE在DEACMP中的作用机制尚不清楚。建立sd - dawley大鼠一氧化碳中毒模型。采用Morris水迷宫（MWM）测试神经功能。采用苏木精和伊红（H&E）染色、尼氏染色、TUNEL染色观察大鼠脑及海马组织病理变化。采用酶联免疫吸附试验（ELISA）评价促炎细胞因子水平。通过相关检测方法测定氧化损伤和细胞凋亡标志物。流式细胞术检测细胞凋亡情况。采用荧光素酶报告和RNA免疫沉淀（RIP）测定来鉴定CRNDE与miR-212-5p的结合关系。CO中毒动物模型和氧糖剥夺（OGD）组CRNDE显著升高，miR-212-5p降低。CRNDE敲低可抑制脑和海马组织的病理损伤和细胞凋亡。此外，CRNDE通过靶向miR-212-5p抑制AKT/GSK3β/β-catenin信号通路。此外，在CO中毒模型中，抑制miR-212-5p可逆转CRNDE沉默对脑组织损伤和凋亡以及AKT/GSK3β/β-catenin信号通路的保护作用。综上所述，在co中毒和ogd处理模型下，CRNDE作为miR-212-5p的“海绵”，通过调节AKT/GSK3β/β-catenin信号通路，加重了脑和海马组织的损伤和凋亡，提示DEACMP是一个选择性的治疗靶点。
Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is the most serious sequel of acute CO poisoning, with structure or function injury of the brain. LncRNA colorectal neoplasia differentially expressed (CRNDE) aberrant expression was involved in nerve cell injury; however, the mechanism of CRNDE in DEACMP remains elusive. CO poisoning model of Sprague–Dawley rats was established. Neurological function was measured by Morris water maze (MWM) testing. Histopathological condition of brain and hippocampus tissues was observed by hematoxylin and eosin (H&E), Nissl, and TUNEL staining. Pro-inflammatory cytokine levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Oxidative damage and apoptosis markers were determined by related detection assays. Cell apoptosis were evaluated by flow cytometry analysis. Luciferase report and RNA immunoprecipitation (RIP) assays were employed to identify the binding relationship of CRNDE and miR-212-5p. CRNDE was significantly increased in CO poisoning animal model and oxygen–glucose deprivation (OGD) group, while that of miR-212-5p was decreased. CRNDE knockdown repressed the histopathological damage and apoptosis of brain and hippocampus tissues. Besides, CRNDE suppressed the AKT/GSK3β/β-catenin signaling pathway via targeting miR-212-5p. Furthermore, the protective effects of CRNDE silencing on brain tissue injury and apoptosis and AKT/GSK3β/β-catenin signaling pathway were reversed by inhibition of miR-212-5p in CO poisoning model. Collectively, CRNDE, serving as a sponge of miR-212-5p, aggravated the injury and apoptosis of brain and hippocampus tissues through regulating AKT/GSK3β/β-catenin signaling pathway under the CO-poisoning and OGD-treated model, suggesting a selected therapeutic target of DEACMP.