Survival of endogenous hepatic stem/progenitor cells in liver tissues during liver cirrhosis
Survival of endogenous hepatic stem/progenitor cells in liver tissues during liver cirrhosis
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肝硬化期间肝组织内源性肝干/祖细胞的存活
DOI：
10.1016/j.lfs.2019.117121
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发表时间：
2020-01-15
期刊：
影响因子：
6.1
通讯作者：
Bai, Lianhua
中科院分区：
文献类型：
--
作者：
Chen, Quanyu;You, Xiaolin;Bai, Lianhua
目的：本研究探讨肝硬化时内源性肝干/祖细胞（HSP）存活是否与损伤信号有关。材料与方法：用二乙基亚硝胺（DEN）饮水诱导C57 BL/6小鼠肝硬化。苏木精-伊红染色和Masson三色染色分别用于识别浸润细胞和结缔组织。炎症活动度分级和纤维化分期，分别用G和S表示，并采用国际简化分级和分期系统（ISGSS）进行评价。通过用抗神经/神经胶质抗原2（Ng2）抗体进行免疫荧光染色来鉴定内源性HSP细胞（Ng2（+）HSP）。使用SPSS 22.0和GraphPad Prism 6分析所有数据，并进行学生t检验以确定统计学显著性。主要发现：所有给予口服DEN的小鼠均发生肝纤维化、肝硬化和肝细胞癌（HCC）。在纤维化期间，观察到内源性HSP（Ng2（+）HSP）细胞的存活与炎症活动呈正相关。随着疾病发展到肝硬化阶段，当内源性HSP细胞与炎症活动失去相关性时，内源性HSP（Ng2（+）HSP）细胞的存活率显著降低。意义：DEN诱导的肝硬化可发展为纤维化、肝硬化和癌症三个时间段，模型的组织学模式与人类相似。内源性HSP（Ng2（+）HSP）细胞的显著存活和较少凋亡在纤维化状态内，其中炎症信号强烈，表明肝硬化期间的这种时间段（1 - 6周）对于动员内源性HSP基再生是重要的。
Aims: This study addressed whether endogenous hepatic stem/progenitor (HSP) cells survival were related to the injured signals during liver cirrhosis.Material and methods: Liver cirrhosis was induced in C57BL/6 mice by administering diethylnitrosamine (DEN) in drinking water. Hematoxylin-eosin staining and Masson's trichrome staining were used to identify infiltrative cells and connective tissues, respectively. The inflammatory activity grade and fibrotic stage, represented as G and S respectively, and evaluated by the International Simplified Grading and Staging System (ISGSS). Endogenous HSP cells (Ng2(+)HSP) were identified by immunofluorescence staining with an anti-neuro/glial antigen 2 (Ng2) antibody. All data were analyzed using SPSS 22.0 and GraphPad Prism 6 and Student's t-test was performed to determine statistical significance. p-values < 0.05 were considered statistically significant.Key findings: All mice administered oral DEN developed liver fibrosis, liver cirrhosis and hepatocellular carcinoma (HCC). During the fibrosis period, observed a positive correlation of survival of endogenous HSP (Ng2(+)HSP) cells with inflammatory activity. As the disease developed into the cirrhotic stage, when lost correlation of endogenous HSP cells with inflammatory activity, revealed a dramatically reduced survival rate of endogenous HSP (Ng2(+)HSP) cells.Significance: The DEN-induced liver cirrhosis could develop into three time zone of fibrosis, cirrhosis and cancer, and the histological patterns in the model are similar to those described in humans. Dramatic survival and less apoptosis of endogenous HSP (Ng2(+)HSP) cells was within fibrotic state, where inflammation signals is strong, indicating such time zone (1-6 weeks) during liver cirrhosis is important for mobilizing endogenous HSP-based regeneration.