microRNA在非酒精性脂肪性肝炎发生发展中的作用

安薪宇; 胡灵溪; 乔杰; 王荣琦; 南月敏

doi:10.3969/j.issn.1001-5256.2021.12.048

microRNA在非酒精性脂肪性肝炎发生发展中的作用

DOI: 10.3969/j.issn.1001-5256.2021.12.048

河北医科大学第三医院中西医结合肝病科，石家庄 050051

基金项目:

2020年政府资助省级临床医学优秀人才培养项目 ;

河北省自然科学基金 (H2021206140)

详细信息

通信作者:
王荣琦，wangrongqiw@163.com

中图分类号: R575.5
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出版历程
- 收稿日期: 2021-05-07
- 录用日期: 2021-07-05
- 出版日期: 2021-12-20

Role of microRNAs in the development and progression of nonalcoholic steatohepatitis

Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang 050051, China

Research funding:

2020 Government-Funded Provincial-Level Clinical Medicine Outstanding Talent Training Project ;

Natural Science Foundation of Hebei Province (H2021206140)

摘要

摘要: 非酒精性脂肪性肝炎(NASH)已经成为肝炎的第二大病因，可进一步进展为肝纤维化、肝硬化甚至肝癌，但其确切发病机制尚不十分清楚，亦缺乏有效的治疗药物。microRNA是体内的一类非编码、转录后调控、高度保守的小分子RNA，在多种肝脏疾病中发挥着重要作用，主要就microRNA在NASH发生发展中的作用作一综述。
- 非酒精性脂肪性肝炎 /
- 微RNAs /
- 病理过程
Abstract: Nonalcoholic steatohepatitis (NASH) has become the second leading cause of hepatitis and can further progress to liver fibrosis, liver cirrhosis, and even liver cancer; however, the detailed pathogenesis of NASH remains unclear, and there is still a lack of effective therapeutic drugs. MicroRNAs (miRNAs) are a class of non-coding, post-transcriptionally regulated, and highly conserved small RNAs in the body and play an important role in a variety of liver diseases. This article mainly reviews the role of miRNAs in the development and progression of NASH.
- Nonalcoholic Steatohepatitis /
- MicroRNAs /
- Pathologic Processes

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图 1 miRNA导致肝损伤的机制

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表 1 miRNA在NASH中的表达

miRNA	表达异常	作用机制	参考文献
miR-155	表达下调	结合LXRα的3′UTR促进肝脂肪生成；增强C/EBP的丰度	[8-11]
miR-122	表达上调	通过上调SREBP-1c、HMG-CoA、SREBP-2影响脂质代谢, 参与线粒体氧化应激	[12-13]
miR-21	表达上调	抑制PPARα的表达，导致脂质堆积；参与菌群失调的调节	[14-15]
miR-375	表达上调	抑制PPARα通路的激活影响肝脏脂质代谢及炎症反应	[16]
miR-34a	表达上调	引起其靶点PPARα和SIRT1的下调，从而导致脂质的异常沉积，激活AMPK途径促进炎症进展	[17-19]
miR-103/107	表达上调	增加脂肪细胞中直接靶基因小窝蛋白1的表达，诱导胰岛素抵抗	[20]
miR-101-3p	表达下调	通过调节胰岛素信号的关键介质来促进胰岛素抵抗	[21]
miR-378	表达上调	阻断AMPK信号通路而增强NF-κB/TNFα轴，增强炎症反应	[22]
miR-223	表达上调	抑制CXCL10和TAZ的表达，影响肝脏炎症	[23]
miR-214-3p	表达上调	抑制线粒体自噬	[24]
miR-192	表达上调	通过激活TGFβ/Smad信号，参与肝纤维化过程	[25]
miR-29	表达下调	参与了胰岛素信号通路、Wnt信号通路、丝裂原活化蛋白激酶信号通路, 抑制UPRmt的激活	[26]
注：SREBP，固醇调节元件结合蛋白；HMG-CoA，3-羟基-3-甲基戊二酰辅酶A；PPAR，过氧化物酶体增殖物激活受体；SIRT，沉默信息调节因子；AMPK，AMP依赖的蛋白激酶；CXCL，趋化因子；TAZ，PDZ结合基序；LXR，肝脏X受体；UTR，非翻译区。

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参考文献(39)

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