Xiang Yan, Pang Bing-Yao, Zhang Yuan, Xie Qiao-Ling, Zhu Ying, Leng Ai-Jing, Lu Long-Qing, Chen Hai-Long
Department of Infectious Diseases, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
Department of Pharmacy, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
Mol Med Rep. 2017 Feb;15(2):613-626. doi: 10.3892/mmr.2016.6083. Epub 2016 Dec 29.
Yi Guan Jian decoction (YGD) may induce the differentiation of bone marrow mesenchymal stem cells (BMSCs) into hepatocyte-like cells (HLCs); however, the underlying mechanisms remain to be elucidated. The present study aimed to investigate this process. To do this, a dimethylnitrosamine (DMN)-induced liver cirrhosis mouse model was established. The mice from the model group were randomly divided into three subgroups: i) Negative control, ii) hepatocyte growth factor and iii) YGD. The overall health, liver function and histological alterations were monitored. The expression of α‑smooth muscle actin (α‑SMA), C‑X‑C chemokine receptor type 4 (CXCR4), extracellular signal‑regulated kinase (ERK1/2), nuclear factor κB p65 subunit (NF‑κB p65) and β‑catenin were measured by immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction. Following administration of DMN, the overall health of the mice significantly decreased, with an increase in pathological developments and liver damage resulting in a decrease in liver function. Immunohistochemistry revealed that the expression of α‑SMA, CXCR4, ERK1/2, NF‑κB p65 and β‑catenin was upregulated. Following treatment with YGD, the overall health, liver function and pathology improved. The mRNA and protein expression levels of CXCR4 and ERK1/2 were upregulated, where as α‑SMA, NF‑κB p65 and β‑catenin levels were downregulated. The results demonstrated that YGD may induce the differentiation of BMSCs into HLCs to reverse DMN‑induced liver cirrhosis; this may be achieved via an upregulation of the SDF‑1/CXCR4 axis to activate the mitogen activated protein kinase/ERK1/2 signaling pathway.
一贯煎（YGD）可能诱导骨髓间充质干细胞（BMSCs）分化为肝细胞样细胞（HLCs）；然而，其潜在机制仍有待阐明。本研究旨在探究这一过程。为此，建立了二甲基亚硝胺（DMN）诱导的肝硬化小鼠模型。模型组小鼠被随机分为三个亚组：i）阴性对照组，ii）肝细胞生长因子组和iii）一贯煎组。监测小鼠的整体健康状况、肝功能和组织学改变。通过免疫组织化学、蛋白质印迹法和逆转录-定量聚合酶链反应检测α-平滑肌肌动蛋白（α-SMA）、C-X-C趋化因子受体4（CXCR4）、细胞外信号调节激酶（ERK1/2）、核因子κB p65亚基（NF-κB p65）和β-连环蛋白的表达。给予DMN后，小鼠的整体健康状况显著下降，病理进展增加，肝损伤导致肝功能下降。免疫组织化学显示α-SMA、CXCR4、ERK1/2、NF-κB p65和β-连环蛋白的表达上调。给予一贯煎治疗后，小鼠的整体健康状况、肝功能和病理学得到改善。CXCR4和ERK1/2的mRNA和蛋白表达水平上调，而α-SMA、NF-κB p65和β-连环蛋白水平下调。结果表明，一贯煎可能诱导BMSCs分化为HLCs以逆转DMN诱导的肝硬化；这可能是通过上调SDF-1/CXCR4轴来激活丝裂原活化蛋白激酶/ERK1/2信号通路实现的。
