首页|LncRNA-NEAT1通过调控 miR-129-5p/HMGB1轴诱导的肝细胞焦亡在急性肝损伤中的机制研究

LncRNA-NEAT1通过调控 miR-129-5p/HMGB1轴诱导的肝细胞焦亡在急性肝损伤中的机制研究

扫码查看
目的 探讨长链非编码RNA核富集转录本1(LncRNA-NEAT1)通过调控miR-129-5p/高迁移率族蛋白1(HMGB1)轴诱导的肝细胞焦亡在急性肝损伤中的作用机制。方法 运用人肝细胞株L02,通过四氯化碳建立肝细胞损伤模型,检测谷丙转氨酶(ALT)和谷草转氨酶(AST)水平评估肝细胞损伤程度,采用CCK-8方法检测细胞增殖活性,检测白细胞介素(IL)-1β和IL-18评估细胞焦亡程度,采用实时荧光定量聚合酶链式反应(RT-PCR)检测LncRNA-NEAT1和miR-129-5p mRNA的表达水平;干扰NEAT1表达,用四氯化碳处理细胞,检测对照组和处理组细胞中ALT、AST、IL-1β、IL-18水平,采用RT-PCR检测LncRNA-NEAT1 和miR-129-5p mRNA的表达水平;干扰NEAT1表达后,转染miR129-5p mimics,用四氯化碳处理细胞,检测对照组和处理组细胞中ALT、AST、IL-1β、IL-18水平,采用RT-PCR检测LncRNA-NEAT1和miR-129-5p mRNA的表达水平;采用双荧光素酶报告基因实验分别验证NEAT1与miR-129-5p、miR-129-5p与HMGB1的关系。结果 四氯化碳处理细胞后,肝细胞中ALT和AST水平显著增加,IL-1β和IL-18表达水平升高,细胞活性下降,NEAT 1表达升高,miR-12 9-5 p表达抑制,差异均有统计学意义(P<0。05);干扰NEAT1后,肝细胞中ALT、AST、IL-1β、IL-18水平下降,miR-129-5p表达显著增加,差异均有统计学意义(P<0。05);干扰NEAT1再转染miR-129-5p mimic后,抑制了肝细胞中ALT、AST、IL-1β、IL-18水平,减弱了 NEAT1表达,增加了 miR-129-5p表达,差异均有统计学意义(P<0。05);NEAT1靶向调控miR-129-5p表达,miR-129-5p靶向作用于HMGB1。结论 干扰NEAT1可能靶向调控miR-129-5p/HMGB1轴抑制在四氯化碳诱导的急性肝损伤中肝细胞的焦亡。
Study on the mechanism of hepatocyte pyroptosis induced by LncRNA-NEAT1 regulation of the miR-129-5p/HMGB1 axis in acute liver injury
Objective To investigate the mechanism of long non-coding RNA nuclear-enriched abundant transcript 1(LncRNA-NEAT1)in inducing hepatocyte pyroptosis in acute liver injury through the regulation of the miR-129-5p/high mobility group box 1(HMGB1)axis.Methods Human hepatocyte line L02 was used to establish a model of hepatocyte injury induced by carbon tetrachloride(CCl4).Alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were measured to assess the degree of hepatocyte injury.Cell proliferation activity was detected using the CCK-8 method,and interleukin(IL)-1β and IL-18 levels were measured to evaluate the extent of cell pyroptosis.Real-time quantitative polymerase chain reaction(RT-PCR)was used to detect the expression levels of LncRNA-NEAT1 and miR-129-5p mRNA.After interfering with NEAT1 expression and treating cells with CCl4,ALT,AST,IL-1β,and IL-18 levels were measured in the control and treatment groups,and RT-PCR was used to detect the expression levels of LncRNA-NEAT1 and miR-129-5p mRNA.After interfering with NEAT1 expression,miR-129-5p mimics were transfected,and cells were treated with CCl4.ALT,AST,IL-1β,and IL-18 levels were measured in the control and treatment groups,and RT-PCR was used to detect the expression levels of LncRNA-NEAT1 and miR-129-5p mRNA.Dual-luciferase reporter gene assays were performed to verify the relationship between NEAT1 and miR-129-5p,and miR-129-5p and HMGB1,respectively.Results After CCl4 treatment,ALT and AST levels in hepato-cytes increased significantly,IL-1β and IL-18 expression levels increased,cell activity decreased,NEAT1 ex-pression increased,and miR-129-5p expression was inhibited,with statistically significant differences(P<0.05).After NEAT1 interference,ALT,AST,IL-1β,and IL-18 levels in hepatocytes decreased,and miR-129-5p expression increased significantly,with statistically significant differences(P<0.05).After NEAT1 inter-ference and miR-129-5p mimic transfection,ALT,AST,IL-1β,and IL-18 levels in hepatocytes were inhibited,NEAT1 expression was reduced,and miR-129-5p expression was increased,with statistically significant differ-ences(P<0.05).NEAT1 targetedly regulated miR-129-5p expression,and miR-129-5p targeted HMGB1.Conclusion Interfering with NEAT1 may inhibit hepatocyte pyroptosis in CCl4-induced acute liver injury by targeting the miR-129-5p/HMGB1 axis.

LncRNA-NEAT1miR-129-5pHigh mobility group box 1HepatocytePyropto-sisAcute liver injury

吴杨荷、蔡福景、徐霜、周克

展开 >

温州医科大学附属第三医院/瑞安市人民医院感染科,浙江瑞安 325200

长链非编码RNA核富集转录本1 miR-129-5p 高迁移率族蛋白1 肝细胞 焦亡 急性肝损伤

浙江省温州市科技局基础性医疗卫生科技项目

Y2020936

2024

现代医药卫生
重庆市卫生信息中心

现代医药卫生

影响因子:0.758
ISSN:1009-5519
年,卷(期):2024.40(18)