miR-122在骨髓间充质干细胞治疗大鼠急性肝损伤中的作用

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1 d，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。%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.