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外泌体在肝内胆管癌中的作用
DOI: 10.12449/JCH240130
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：唐晋元负责课题设计与论文撰写；杨陈凤麟、梁冬乐负责绘制表格与图片；罗雨豪负责思路设计，文章修改和最后定稿。
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摘要: 肝内胆管癌（ICC）是一种特殊类型的肝癌，其早期临床症状不典型，大多数患者初诊时已处于中晚期。由于缺乏有效的分子标志物和治疗手段，ICC患者5年生存率极低。外泌体是一种细胞分泌的囊泡，包含蛋白质、RNA、脂质等，是细胞间通讯的重要载体。近期研究显示外泌体在ICC发生发展过程中扮演重要角色，本文就外泌体在ICC中的诊断、治疗作用及其机制进行综述，并展望外泌体的治疗前景与潜在的临床应用。Abstract: Intrahepatic cholangiocarcinoma （ICC） is a special type of liver cancer with atypical clinical symptoms in the early stage， and most patients are already in the advanced stage at the time of initial diagnosis. Due to a lack of effective molecular markers and treatment options， ICC patients tend to have an extremely low five-year survival rate. Exosomes are vesicles secreted by cells that contain proteins， RNA， and lipids， and they are important carriers of intercellular communication. Recent studies have shown that exosomes play a crucial role in the development and progression of ICC， and this article reviews the role and mechanism of exosomes in the diagnosis and treatment of ICC and looks into the future treatment prospect and potential clinical application of exosomes.
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Key words:
- Cholangiocarcinoma /
- Exosomes /
- Diagnosis /
- Therapeutics
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图 2 ICC的分子发病机制
注： EVCOX，环加氧酶；CTLA-4，细胞毒性T淋巴细胞抗原4；CXCL，C-X-C基序趋化因子配体；EGF，表皮生长因子；ERK，细胞外信号调节激酶；Hh，刺猬通路；IDH，异柠檬酸脱氢酶；iNOS，诱导氮氧化物合酶；MMP，基质金属蛋白酶；NF-κB，核因子κB；PDGF，血小板衍生生长因子；PD-1，程序性死亡蛋白1；PD-L1，程序性死亡配体1；PGE，前列腺素E；PI3K，磷脂酰肌醇3-激酶；STAT3，信号传导和转录因子3；TAM，肿瘤相关巨噬细胞；TAN，肿瘤相关性中性粒细胞。
Figure 2. Molecular pathogenesis of cholangiocarcinoma
图 3 ICC源性外泌体调节肿瘤进展的机制
Figure 3. ICC derived exosomes can regulate tumor progression through a variety of mechanisms
图 4 外泌体在ICC与CAF细胞通信中的作用
Figure 4. Effects of exosomes on the interaction between ICC and CAF cells
表 1 外泌体与其他传统细胞外囊泡的区别
Table 1. Differences between exosomes and other traditional extracellular vesicles
特征 直径（nm） 密度（g/mL） 形状 组成 标志物 细胞内起源 外泌体 40～100 1.13～1.19 杯状 胆固醇，鞘磷脂，神经酰胺，脂筏，暴露PPS CD63，CD9，Alix， TSG101 内部隔室 （核内体） 微泡 100～1 000 不规则形状 暴露PPS 整合素，选择素 和CD40配体 质膜 核外颗粒体 50～200 双圆形 胆固醇，二酰基甘油，PPS CR1和蛋白水解酶 质膜 膜颗粒 50～80 1.04～1.07 圆形 CD133 质膜 外泌体样颗粒 20～50 1.1 不规则形状 无脂筏 TNFR I 凋亡小泡 50～500 1.16～1.28 异形 组蛋白 
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