骨髓间充质干细胞移植后在肝损伤大鼠体内的分布及其治疗作用

Distributionand therapeutic effect of transplanted bone marrow mesenchymal stem cells(MSCs) in rats with liver injury

目的探讨同种异体骨髓间充质干细胞(MSCs)移植后在大鼠体内的分布及其对肝损伤的治疗作用。方法应用2-乙酰氨基芴(2-AAF)建立大鼠急性肝损伤模型,经门静脉注射进行同种异体骨髓MSCs移植后不同时间,通过4,6-二醚基-2-苯基吲哚盐酸化合物(DAPI)标记、免疫组化Y染色体性别决定区(SRY)检测等方法观察移植细胞分布,并通过肝组织病理改变和丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)和血清白蛋白(ALB)的变化观察MSC移植对肝损伤的治疗作用。结果 2-AAF可导致大鼠肝组织弥漫性损伤,移植后1 w和3 w肝组织病变减轻。移植后1 w受体鼠肝、肺及脾脏中均可见DAPI阳性细胞,移植后3 w仅在肝损伤大鼠肝内发现DAPI阳性细胞组成的细胞簇,形态与肝实质细胞相近;SRY蛋白检测结果与之一致。干细胞移植后1 w,移植组大鼠血清ALT较移植前显著降低,但仍高于对照组;血清AST较移植前显著降低,且与对照组无显著差异;血清ALB较移植前增高,但仍显著低于对照组。干细胞移植后3 w,ALT、AST以及ALB均与对照组无显著差异。结论 2-AAF可造成大鼠肝组织弥漫性损伤,肝损伤环境有助于经门静脉移植的骨髓MSCs的定植,MSCs移植对大鼠肝损伤具有治疗作用。

Objective This study focused on whether the transplantation of bone marrow mesenchymal stem cells （MSCs） as allograft can improve the liver function and to clarify the distribution of these trans- planted MSCs in rats. Methods orene （2 - AAF）. MSCs obtained Rat model from male of acute liver injury was established with 2 - acetylaminoflu- rats were transplanted into the female rat liver via the portal vein. The changes of serum ALB, ALT and AST were detected. The distributions of transplanted MSCs were observed by fluorescence labeling and immunohistochemistry. Results 2 - AAF induced diffuse hepatic injury. The distribution of transplanted bone marrow MSCs was as follows： One week after trans- plantation, DAPI - positive cells were dispersed in the liver, lung and spleen. But positive cells could be found only in the injured liver 3 weeks after transplantation. These cells were in clusters and phenotypically resembled hepatocytes. SRY protein could be detected in the liver, lung and spleen at one week after transplantation, but could only be detected in the injured livers 3 weeks after transplantation. One week after transplantation, AST was decreased but was still higher than that of the control group. ALT was also decreased and had no significant difference compared with that of the control group. ALB was in- creased but was still lower than that of the control group. Three weeks after transplantation, ALT, AST and ALB were all in normal range. Conclusions Large -dose of 2 -AAF can cause diffuse hepatic inju- ry. Portal vein injection of bone marrow MSCs can improve to some extent rat liver injury induced by 2 - AAF. The microenvironment of injured liver may contribute to the distribution of bone marrow MSCs trans- planted via the portal vein. Transplantation of bone marrow MSCs has certain therapeutic effect on liver in- jury.