miR-122在骨髓间充质干细胞治疗大鼠急性肝损伤中的作用

doi:10.13481/j.1671-587x.20150610

吉林大学学报(医学版) ›› 2015, Vol. 41 ›› Issue (06): 1150-1153.doi: 10.13481/j.1671-587x.20150610

miR-122在骨髓间充质干细胞治疗大鼠急性肝损伤中的作用

赵民学¹, 李柏文¹, 王德盛², 曹宏³

1. 吉林医药学院附属医院普外科, 吉林吉林 132013;
2. 第四军医大学西京医院肝胆外科, 陕西西安 710032;
3. 吉林大学中日联谊医院普外3科, 吉林长春 130033

收稿日期:2015-08-18 发布日期:2016-01-11
通讯作者: 王德盛,主任医师,博士研究生导师(Tel:029-84775259,E-mail:wangdesh@163.com);曹宏,主任医师,硕士研究生导师(Tel:0431-84997753,E-mail:caohong1967@163.com) E-mail:wangdesh@163.com;caohong1967@163.com
作者简介:赵民学(1981-),男,吉林省吉林市人,主治医师,医学硕士,主要从事普通外科疾病基础及临床治疗方面的研究。
基金资助:
国家自然科学基金资助课题(30872480)

Role of miR-122 in bone marrow derived stem cell therapy for acute liver injuryin rats

ZHAO Minxue¹, LI Bowen¹, WANG Desheng², CAO Hong³

1. Department of General Surgery, Affiliated Hospital, Jilin Medical College, Jilin 132013, China;
2. Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China;
3. Department of General Surgery, China-Japan Union Hospital, Jilin University, Changchun 130033, China

Received:2015-08-18 Published:2016-01-11

摘要/Abstract

摘要：

目的:探讨miR-122在骨髓间充质干细胞(BMSCs)治疗大鼠急性肝损伤中的作用,阐明相关作用机制。方法:密度梯度离心法分离收集雄性大鼠的BMSCs,分为转染组和对照组,其中转染组BMSCs采用脂质体介导转染miR-122 mimics,对照组BMSCs未接受转染。将60只四氯化碳(CCl₄) 诱导的急性肝损伤大鼠随机分为肝损伤对照组(静脉注射生理盐水)、普通治疗组(静脉移植普通BMSCs)和实验治疗组(静脉移植转染miR-122的BMSCs)(n=20)。移植细胞后1、7和14 d检测大鼠肝功能,肝组织行HE染色观察其病理学改变。结果:转染miR-122 mimics后7 d,BMSCs中白蛋白(ALB)表达水平明显上调,而甲胎蛋白(AFP)的表达水平则明显下调。移植细胞后1d,与普通治疗组比较,实验治疗组血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)活性差异无统计学意义(P>0.05);移植细胞后7和14 d时,实验治疗组大鼠血清ALT和AST活性均低于普通治疗组(P<0.05);HE染色,实验治疗组大鼠肝脏充血、细胞质内空泡变性及肝细胞坏死情况明显好于普通治疗组。结论:上调BMSCs中miR-122表达水平能够促进其分化为肝样细胞,并可明显改善CCl₄所致大鼠肝脏损伤。

关键词: 骨髓间充质干细胞, miR-122, 细胞移植, 肝损伤

Abstract:

Objective To investigatet the effects of miR-122 in the therapy of bone marrow derived stem cells (BMSCs) for acute liver injury in the rats, and to clarify the mechanism. Methods The BMSCs were isolated from the bone marrow of male rats by density gradient centrifugation. The BMSCs were divided into transfection group and control group. The BMSCs in transfection group were transfected with miR-122 mimics by liposome, while the BMSCs in control group were not. 60 SD rats with acute liver injury induced by 10%CCl₄ were randomly divided into control group (the saline was injected through mainline), normal treatment group (the normal BMSCs were injected through mainline) and experimental therapy group (the BMSCs transfected with miR-122 mimics by liposome were injected through mainline) (n=20).The liver function and tissue pathology were examined at 1 d, 7 d and 14 d after transplantation. Results The expression level of ALB in BMSCs was up-regulated, while the AFP expression level was down-regulated after the transfection of miR-122 mimics. At 1 d after transfection of BMSCs, the serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) activities had no significant difference between normal treatment group and experimental therapy group. At 7 d and 14 d after transfection of BMSCs, the serum ALT and AST activities in experimental therapy group were obviously lower than those in normal treatment group (P<0.05). The liver congestion,cytoplasm degeneration and liver cell necrosis in experimental therapy group were improved compared with normal treatment group. Conclusion The up-regulation of miR-122 expression in BMSCs would promote its differentiation into hepatocyte like cells, which plays a role in promoting the recovery of liver injury.

Key words: bone marrow derived stem cells, miR-122, cell transplantation, liver injury

中图分类号:

R657.3

赵民学, 李柏文, 王德盛, 曹宏. miR-122在骨髓间充质干细胞治疗大鼠急性肝损伤中的作用[J]. 吉林大学学报(医学版), 2015, 41(06): 1150-1153.

ZHAO Minxue, LI Bowen, WANG Desheng, CAO Hong. Role of miR-122 in bone marrow derived stem cell therapy for acute liver injuryin rats[J]. Journal of Jilin University Medicine Edition, 2015, 41(06): 1150-1153.

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miR-122在骨髓间充质干细胞治疗大鼠急性肝损伤中的作用

Role of miR-122 in bone marrow derived stem cell therapy for acute liver injuryin rats

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