骨髓间充质干细胞移植对严重烧伤大鼠肝损伤的修复作用及其机制

doi:10.13481/j.1671-587x.20140201

吉林大学学报(医学版)

• 基础研究 • 下一篇

骨髓间充质干细胞移植对严重烧伤大鼠肝损伤的修复作用及其机制

陈浩¹，尹飞²，孟春阳²，周煜博¹，张颖¹，秦永刚¹，杨小玉²，郭丽^1

（1.吉林大学公共卫生学院卫生毒理学教研室,吉林长春 130021；2.吉林大学中日联谊医院骨科，吉林长春 130033）

收稿日期:2013-07-17 出版日期:2014-03-28 发布日期:2014-03-28
通讯作者: 郭丽 E-mail:E-mail: gli@jlu.edu.cn
作者简介:陈浩(1986-),男,山东省邹城市人,在读医学硕士,主要从事干细胞基础和应用的研究。
基金资助:
国家自然科学基金资助课题( 30972153/ C180103);吉林省科技厅科技发展计划项目资助课题(20130413023GH)；吉林大学基本科研业务费项目-科学前沿与交叉学科创新项目资助课题( 200903114)

Repair effect of transplantation of bone marrow mesenchymal stem cells on liver injury in severe burned rats and its mechanism

CHEN Hao¹,YIN Fei²,MENG Chun-yang²,ZHOU Yu-bo¹,ZHANG Ying¹,QIN Yong-gang¹,YANG Xiao-yu²,GUO Li¹

(1.Department of Hygienic Toxicology,School of Public Health,Jilin University,Changchun 130021,China;2. Department of Orthopedics,China-Japan Union Hospital,Jilin University,Changchun 130033,China)

Received:2013-07-17 Online:2014-03-28 Published:2014-03-28

摘要/Abstract

摘要：

目的：探讨骨髓间充质干细胞（BMSCs）移植对严重烧伤大鼠肝损伤的修复作用，初步阐明其作用机制。方法：体外分离、培养、扩增、鉴定并标记大鼠BMSCs。将30只Wistar大鼠随机分成正常对照组、模型组和细胞治疗组,每组10只。制备大鼠烧伤模型，将氯甲基苯甲酰胺（CM-Dil）标记的BMSCs经球后静脉移植到细胞治疗组大鼠体内，模型组大鼠注射生理盐水。观察各组大鼠的一般状况。细胞移植后2周取大鼠肝组织，进行病理组织学观察和评分；TUNEL法检测肝细胞凋亡率；激光共聚焦显微镜观察BMSCs在大鼠肝组织中的定植情况。结果：细胞移植后2周，模型组大鼠精神明显萎靡、少动；细胞治疗组大鼠精神状态较好，大鼠体质量显著高于模型组（P<0.05）。病理组织学观察，模型组大鼠肝小叶结构消失，肝索排列紊乱，部分肝窦扩张充血，散在淋巴细胞浸润，偶见小灶性聚集，肝细胞浊肿，有些细胞胞浆疏松，脂肪变性；细胞治疗组大鼠肝组织的病理学改变较轻，明显好于模型组；细胞治疗组大鼠病理组织学评分明显低于模型组(P<0.05)。TUNEL法检测，模型组大鼠肝组织出现较多凋亡肝细胞，细胞治疗组大鼠肝细胞凋亡率明显低于模型组（P<0.05）。激光共聚焦显微镜观察，细胞治疗组大鼠肝组织中有CM-Dil标记的BMSCs。结论：BMSCs移植后能够向受损肝组织定植，对烧伤引起的肝损伤有明显的修复作用，其机制可能与抑制细胞凋亡有关。

关键词: 骨髓间充质干细胞, 烧伤, 肝损伤, 细胞移植, 修复

Abstract:

Abstract:Objective
To investigate the repair effect of transplantation of bone marrow mesenchymal stem cells (BMSCs) on liver injury in severe burned rats,and to clarify its mechanism.Methods The BMSCs of rats were isolated,cultured,amplified,identified,and labeled in vitro.30 Wistar rats were randomly divided into normal control group(n=10),model group(n=10) and cell therapy group(n=10).The burned rat model was established.The BMSCs labeled by chlormethyl-benzamidodialkylcarbocyanine(CM-Dil) were transplanted into the rats in cell therapy group by retro-orbital intravenous injection and the saline was injected into the rats in model group.The general status of all rats were observed.The liver tissues of rats were obtained 2 weeks after transplantation,and the pathohistological changes were observed and the pathohistological scores were detected;the apoptotic rate of liver cells was detected by TUNEL method;the engraftment of BMSCs in liver tissues of the rats was observed under laser scanning confocal microscope.Results 2 weeks after transplantation,the rats in model group were obviously malaise dispirited and the rats in cell therapy group showed obviously better,and the body weight of the rats in cell therapy group was higher than that in model group(P<0.05).The pathohistological results showed the normal liver lobules of the rats in model group disappeared,and the liver cords disordered,and some liver sinusoids dilated and congested,lymphocytes infiltrated with occasional focal aggregating,and cell edema was found,cytoplasm loose and steatosis were seen in liver tissue.However,the pathohistological changes of liver tissue of the rats in cell therapy group were significantly better than those in model group.The pathohistological score of the rats in cell therapy group was significantly lower than that in model group(P<0.05).The TUNEL staining results showed that there were lots of apoptotic liver cells in liver tissue of the rats in model group,and the apoptotic rate of liver cells in cell therapy group was significantly lower than that in model group(P<0.05).CM-Dil labeled BMSCs were found in liver tissue of the rats in cell therapy group under confocal microscope.Conclusion BMSCs can implant into the damaged liver tissue after transplantation,and BMSCs have an obvious repair effect on liver injury caused by burning,and the possible mechanism may be associated with the inhibiting of apoptosis.

Key words: bone marrow mesenchymal stem cells, burning, liver injury, cell transplantation, repairment

中图分类号:

陈浩，尹飞，孟春阳，周煜博，张颖，秦永刚，杨小玉，郭丽. 骨髓间充质干细胞移植对严重烧伤大鼠肝损伤的修复作用及其机制[J]. 吉林大学学报(医学版), 2014, 40(02): 219-223.

CHEN Hao,YIN Fei,MENG Chun-yang,ZHOU Yu-bo,ZHANG Ying,QIN Yong-gang,YANG Xiao-yu,GUO Li. Repair effect of transplantation of bone marrow mesenchymal stem cells on liver injury in severe burned rats and its mechanism[J]. Journal of Jilin University Medicine Edition, 2014, 40(02): 219-223.

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骨髓间充质干细胞移植对严重烧伤大鼠肝损伤的修复作用及其机制

Repair effect of transplantation of bone marrow mesenchymal stem cells on liver injury in severe burned rats and its mechanism

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