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摘要: 微RNA(microRNAs，miRNAs)可稳定存在于细胞、组织及血液中，参与多种疾病的病理过程，成为多种疾病诊断的潜在生物标志物。已有研究表明，其在各种慢性肝病所致的肝纤维化中发挥重要作用，可通过调节肝纤维化相关基因的表达，干预肝纤维化发展进程。本文就miRNA在肝纤维化中的作用机制作一综述，以期为肝纤维化的诊断及分子靶向治疗提供借鉴。Abstract: MicroRNAs(miRNAs) are involved in the pathophysiological processes of many diseases. Stably present in cells, tissues and blood, they can be used as potential markers of many diseases. They play an important role in the pathogenesis of liver fibrosis caused by various chronic liver diseases. It has been shown that miRNAs can participate in the process of liver fibrosis by targeting the down-regulation of liver fibrosis-related gene expression. In this review, we discuss the research progress on the role of miRNAs in liver fibrosis, with the hope of providing reference for diagnosis and molecularly targeted treatment.
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Key words:
- liver fibrosis /
- microRNAs /
- therapeutic strategies /
- targeted delivery
作者贡献：黄璐、吴有斌、刘梦媛负责论文撰写；倪毅然负责论文构思；吴江锋、张艳琼负责论文修订。利益冲突：所有作者均声明不存在利益冲突 -
图 1 肝纤维化相关miRNAs作用靶点
TGF：转化生长因子；Gramlin：骨形态形成蛋白拮抗家族；LOX：赖氨酰氧化酶；Itga：整合素家族；Acot 4：酰基辅酶A硫酯酶4；Menin：MEN1基因的表达产物；COL：胶原蛋白；PDGFC：血小板衍生生长因子C；P4HA1：脯氨酰4-羟化酶亚基α-1；FN1：纤连蛋白1；c-Abl：非受体酪氨酸激酶Abelson超家族成员；SHIP1：含SH2结构域的肌醇5-磷酸酶；PPAR：过氧化物酶体增殖物激活受体；Twist：转录因子蛋白；ACSL：酰基辅酶A合成酶长链蛋白；SIRT1：NAD+依赖的蛋白去乙酰化酶；TGIF2：TGF-β诱导因子同源异构体2；CAV：小窝蛋白；CDKN：细胞周期蛋白依赖性激酶抑制剂；TIMP：组织基质金属蛋白酶抑制剂；PTEN：抑癌基因；E-cad：上皮细胞钙粘素
表 1 肝纤维化相关miRNAs
miRNAs 类别 染色体定位 种子序列 细胞类型 疾病模型 表达水平 miR-23[9, 46-47] 抗肝纤维化 19p13.12;
9q22.32UCACAUU;
UCACAGU;
GGCUCAGHSCs；肝细胞；
胆管上皮细胞CCl4引起的肝纤维化、NASH；硬化性胆管炎 CHC患者血清中下降 miR-29[12-14] 抗肝纤维化 7q32.3；
1q32.2AGCACCA HSCs; CCl4等多种肝纤维化模型 CHC患者血清中上升，与肝纤维化程度呈正相关 miR-122[17-24] 抗肝纤维化 18q21.31 GGAGUGU 肝细胞；HSCs NAFLD CHC患者血清中上升，与肝纤维化程度呈正相关 miR-34[24-29, 48-51] 促肝纤维化 1p36.22;
11q23.1GGCAGUG HSCs；肝细胞；
胆管上皮细胞CCl4等多种肝纤维化模型；原发性胆管炎；NASH CHC患者血清中上升，与肝纤维化程度呈正相关 miR-199[30-32] 促肝纤维化 19p13.2;
1q24.3;
9q34.11CCAGUGU;
CAGUAGUHSCs CCl4等多种肝纤维化模型 CHC患者血清中上升，与肝纤维化程度呈正相关 miR-221/222[34-40] 促肝纤维化 Xp11.3 GCUACAU HSCs；肝细胞；
巨噬细胞CCl4等多种肝纤维化模型 多种肝纤维化模型组织表达上升 miR-155[41-45] 双向作用 21q21.3 UAAUGCU 巨噬细胞；淋巴细
胞；HSCs；肝细胞酒精性脂肪性肝炎和多种肝纤维化模型; 血清中上升，与肝纤维化程度呈正相关 HSCs：肝星状细胞；CCl4: 四氯化碳；NASH：非酒精性脂肪性肝炎；CHC：慢性丙型肝炎；NAFLD：非酒精性脂肪性肝病；AGTR：血管紧张素Ⅱ受体；TCF4：T细胞因子4 
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