人脐带间充质干细胞对类噬血细胞性淋巴组织细胞增多症小鼠模型肝脏损伤的修复作用及机制

刘志娟; 安曦洲; 肖莉; 孟岩; 崔颖慧; 梁绍燕; 于洁

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人脐带间充质干细胞对类噬血细胞性淋巴组织细胞增多症小鼠模型肝脏损伤的修复作用及机制

基础医学 | 更新时间：2026-01-09

- 人脐带间充质干细胞对类噬血细胞性淋巴组织细胞增多症小鼠模型肝脏损伤的修复作用及机制
- Human umbilical mescenchymal stem cells in treatment of hepatotoxicity in hemophagocytic lymphohistocytosis-like mouse model: effect and possible mechanism
- 陆军军医大学学报 2016年38卷第17期页码：1929-1936
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  中图分类号： R392.2;R551.1;R575.05
- 纸质出版：2016
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刘志娟,安曦洲,肖莉,孟岩,崔颖慧,梁绍燕,于洁.人脐带间充质干细胞对类噬血细胞性淋巴组织细胞增多症小鼠模型肝脏损伤的修复作用及机制[J].陆军军医大学学报(原第三军医大学学报),2016,38(17):1929-1936.

　Liu Zhijuan,An Xizhou,Xiao Li,Meng Yan,Cui Yinghui,Liang Shaoyan,Yu Jie.Human umbilical mescenchymal stem cells in treatment of hepatotoxicity in hemophagocytic lymphohistocytosis-like mouse model: effect and possible mechanism[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(17):1929-1936.
刘志娟,安曦洲,肖莉,孟岩,崔颖慧,梁绍燕,于洁.人脐带间充质干细胞对类噬血细胞性淋巴组织细胞增多症小鼠模型肝脏损伤的修复作用及机制[J].陆军军医大学学报(原第三军医大学学报),2016,38(17):1929-1936. DOI：

　Liu Zhijuan,An Xizhou,Xiao Li,Meng Yan,Cui Yinghui,Liang Shaoyan,Yu Jie.Human umbilical mescenchymal stem cells in treatment of hepatotoxicity in hemophagocytic lymphohistocytosis-like mouse model: effect and possible mechanism[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(17):1929-1936. DOI：

摘要

目的探讨人脐带间充质干细胞（human umbilical cord mesenchymal stem cells，hUC-MSCs）对类噬血细胞性淋巴组织细胞增多症（hemophagocytic lymphohistocytosis，HLH）小鼠模型肝脏损伤的修复作用及相关机制。方法采用hUCMSCs的体外标记，将成年野生型C57BL/6小鼠54只

按完全随机方法分为模型损伤组（PBS组）、干细胞治疗组（MSC组）、正常对照组（CON组）。类HLH小鼠模型采用CPGODN1826联合IFN-γ诱导产生，MSC组治疗采用hUCMSCs经尾静脉移植。观察移植后第1、3、7天小鼠一般情况，血生化(ALT、AST、ALB、TG)，外周血三系（WBC、RBC、PLT、HGB）变化，第7天肝质量体质量比，HE染色观察肝脏组织病理变化，免疫组化法观察第7天肝脏中活化巨噬细胞的数量

荧光显微镜观察MSC组CMDil标记的hUCMSCs的肝内定植，免疫荧光法观察第7天MSC组肝脏中抗人白蛋白抗体阳性细胞的数量。结果与PBS组相比，MSC组小鼠的状态好转，肝质量体质量比显著下降（P0.05）；ALT、AST、TG显著降低（P0.05），ALB无明显升高（P0.05），WBC、PLT、RBC、HGB显著升高（P0.05）；肝脏炎症浸润减少、肝组织损伤恢复；肝脏中活化巨噬细胞数量明显减少（P0.05）；肝脏中均可发现有CMDil标记的hUCMSCs的定植，且无人白蛋白的表达。结论 CM-Dil标记的hUC-MSCs经尾静脉移植可以在类HLH小鼠受损的肝脏中定植，并可改善肝功能、修复肝结构、降低活化巨噬细胞的数量，且不是通过hUCMSCs肝样转化实现的。

Abstract

Objective To determine the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) in the treatment of hepatotoxicity in hemophagocytic lymphohistocytosis (HLH)-like mouse model and investigate the possible mechanism. Methods hUC-MSCs were stained with CM-Dil fluorescent carbocyanite in vitro. A total of 54 adult C57BL/6 mice were randomly assigned to the model injury group (PBS group)

stem cell transplantation group (MSC group) and normal control group (CON group). The HLH-like mouse model was induced by CPG oligodeoxynucleotide (CPG-ODN 1826) and interferon (IFN)-γ. Then the CM-Dil-labeled hUC-MSCs were transplanted into the mice of the MSC group via caudal vein. The general conditions were observed in all the mice in 1

3 and 7 d after transplantation. The blood samples in the above 3 time points were collected to measure the serum contents of aspartate transaminase (AST)

alanine transaminase (ALT)

albumin (ALB) and triglyceride (TG)

counts of platelets (PLT)

white blood cells (WBC) and red blood cells (RBC)

and level of hemoglobin (HGB). In 7 d after transplantation

liver weight was determined

the pathohistological changes were observed with hematoxylin-eosin staining

and the number of activated macrophages was tested by immunohistochemical assay. Fluorescent microscopy was used to observe the localization of labeled hUC-MSCs in the liver

and immunofluorescence assay was employed to count the cells positive to anti-human albumin antibody. Results When compared with the PBS group

the mice in the MSC group showed obviously better general condition

decreased ratio of liver weight to body weight (P0.05)

decreased contents of AST

ALT

and TG (P0.05)

no obvious change in the ALB content (P0.05)

and elevated counts of WBC

PLT

RBC and HGB (P0.05). There were less lymphocytes infiltration in the liver

reduced activated macrophages (P0.05)

no expression of human ALB

and attenuated liver damage after hUC-MSCs transplantation. The CM-Dil labeled hUC-MSCs were found in the liver tissue of the MSC group after transplantation. Conclusion The CM-Dil labeled hUC-MSCs are implanted into the damaged liver tissue by caudal vein transplantation. The transplantation improves liver function

repairs injured liver tissue

and reduces activated macrophages

which are not through the MSCs-derived hepatocytelike cells.

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