文章摘要
miR-223/Fosl2/NGP调控非酒精性脂肪性肝炎小鼠肝纤维化作用
The regulatory effect of miR-223/Fosl2/NGP on liver fibrosis in mice with non-alcoholic steatohepatitis
投稿时间：2021-09-07  
DOI：10.3969/j.issn.1000-0399.2022.04.001
中文关键词: 脂肪性肝炎,非酒精性  肝纤维化  微小RNA223  FOS样抗原2  中性粒细胞颗粒蛋白
英文关键词: Non-alcoholic steatohepatitis  Liver fibrosis  MicroRNA223  FOS-like antigen 2  Neutrophil granule protein
基金项目:河南省科技攻关计划项目（项目编号:LHGJ20190531，LHGJ20190532）
作者单位
王航宇 475001 河南开封 河南大学第一附属医院消化病联合微创病区 
杨文义 475001 河南开封 河南大学第一附属医院消化病联合微创病区 
韩大正 475001 河南开封 河南大学第一附属医院消化病联合微创病区 
魏书堂 475001 河南开封 河南大学第一附属医院消化病联合微创病区 
武利萍 475001 河南开封 河南大学第一附属医院消化病联合微创病区 
徐梦阳 475001 河南开封 河南大学第一附属医院消化病联合微创病区 
闫春晓 475001 河南开封 河南大学第一附属医院消化病联合微创病区 
谭莉霞 475001 河南开封 河南大学第一附属医院消化病联合微创病区 
董勇 475001 河南开封 河南大学第一附属医院消化病联合微创病区 
杨国威 475001 河南开封 河南大学第一附属医院消化病联合微创病区 
华静 475001 河南开封 河南大学第一附属医院消化病联合微创病区 
杜莹莹 475001 河南开封 河南大学第一附属医院消化病联合微创病区 
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中文摘要:
      目的 探讨miR-223/ FOS样抗原2（Fosl2）/中性粒细胞颗粒蛋白（NGP）通路调控非酒精性脂肪性肝炎（NASH）小鼠肝纤维化的作用。方法 将60只小鼠随机分成正常组、蛋氨酸胆碱缺乏（MCD）组、MCD+miR-NC组（MCD模型鼠经尾静脉注射120 nmol/kg miR-NC 100 μL）和MCD+miR-223 mimic组（MCD模型鼠经尾静脉注射120 nmol/kg miR-223 mimic 100 μL），每组15只。正常组给予普通饲料，其余组给予 MCD 饲料。酶联免疫吸附法检测4组小鼠血清总胆固醇（TC）、三酰甘油（TG）、谷丙转氨酶（ALT）和谷草转氨酶（AST）水平；采用放射免疫分析法检测小鼠血清透明质酸（HA）、层粘连蛋白（LN）、Ⅳ型胶原（Ⅳ-C）；实时荧光定量PCR检测miR-223和Fosl2 mRNA水平；观察小鼠肝脏病理变化；Western blot检测肝组织Fosl2、NGP蛋白水平。结果 与MCD组和MCD+miR-NC组相比，MCD+miR-223 mimic组中miR-223表达水平升高，Fosl2表达水平下降（P<0.05）。与MCD组和MCD+ miR-NC组相比，MCD+miR-223 mimic组肝细胞空泡化现象减少，肝细胞肥大程度降低。与MCD组和MCD+ miR-NC组相比，MCD+miR-223 mimic组TC、TG、ALT和AST水平下降（P<0.05）。与MCD组和MCD+miR-NC组相比，MCD+miR-223 mimic组中脂质滴减少（P<0.05）。与MCD组和MCD+miR-NC组相比，MCD+miR-223 mimic组HA、LN和Ⅳ-C水平降低（P<0.05）。与MCD组和MCD+miR-NC组相比，MCD+miR-223 mimic组Fosl2蛋白水平下降，NGP蛋白水平上升（P<0.05）。结论 miR-223可能通过调控Fosl2/NGP通路减轻NASH小鼠肝纤维化程度。
英文摘要:
      Objective To explore the regulatory effect of miR-223/FOS-like antigen 2 (Fosl2)/neutrophil granule protein (NGP) pathways on liver fibrosis in mice with non-alcoholic steatohepatitis (NASH). Methods A total of 60 mice were randomly divided into normal group, methionine choline deficiency (MCD) group, MCD+miR-NC group and MCD+miR-223 mimic group, with 15 cases in each group. The normal group was given common feed, while the other groups were given MCD feed. The levels of serum total cholesterol (TC), triglyceride (TG), alanine transaminase (ALT) and aspartate transaminase (AST) were detected by enzyme-linked immunosorbent assay. The levels of serum hyaluronic acid (HA), laminin (LN) and collagen type Ⅳ(Ⅳ-C) were detected by radioimmunoassay. The levels of miR-223 and Fosl2 mRNA were detected by real-time fluorescence quantitative PCR. The pathological changes of liver tissues were observed. The levels of Fosl2 and NGP in liver tissues were detected by Western blot. Results Compared with MCD group and MCD+miR-NC group, the expression level of miR-223 increased, while the expression level of Fosl2 decreased in MCD+miR-223 mimic group (P<0.05). Compared with MCD group and MCD+miR-NC group, the hepatocyte vacuolation was reduced, and hepatocyte hypertrophy was relieved in MCD+miR-223 mimic group. Compared with MCD group and MCD+miR-NC group, the levels of TC, TG, ALT and AST decreased in MCD+miR-223 mimic group (P<0.05). Compared with MCD group and MCD+miR-NC group, lipid droplets were reduced in MCD+miR-223 mimic group (P<0.05). Compared with MCD group and MCD+miR-NC group, the levels of HA, LN and Ⅳ-C decreased in MCD+miR-223 mimic group (P<0.05). Compared with MCD group and MCD+miR-NC group, Fosl2 level decreased, while NGP level increased in MCD+miR-223 mimic group (P<0.05). Conclusion The miR-223 may relieve liver fibrosis in NASH mice by regulating Fosl2/NGP pathways.
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