扶正化瘀方对骨髓细胞在纤维化肝脏中迁移与分化的干预作用  

Migration and differentiation of marrow mononuclear cells in liver fibrosis by Fuzheng Huayu recipe

作　　者：谭烨 刘志强[2] 吕靖[1] 王晓玲[3] 陆雄[2] 刘成海[1,4,5] 

机构地区：[1]上海中医药大学附属曙光医院上海中医药大学肝病研究所,上海201203 [2]上海中医药大学科技实验中心,上海201203 [3]上海中医药大学基础医学院生物学教研室,上海201203 [4]上海市中医临床重点实验室,上海201203 [5]上海中医药大学肝肾疾病病证教育部重点实验室,上海201203

出　　处：《中国中西医结合消化杂志》2013年第4期169-174,共6页Chinese Journal of Integrated Traditional and Western Medicine on Digestion

基　　金：国家中医药管理局中医肝胆病重点学科(2010sh);上海高校中医内科E-研究院建设计划(E03008);上海高校创新团队建设项目(第一期)部分资助

摘　　要：[目的]探究扶正化瘀方(Fuzheng Huayu recipe,FZHY)对骨髓细胞在肝纤维化形成中向肝脏迁移与分化的干预作用。[方法]以绿色荧光蛋白(green fluorescent protein,GFP)标记的供体ICR小鼠的骨髓细胞移植入受体ICR小鼠,8周后进行受体外周血GFP鉴定,并分为移植后对照组与移植后模型组,移植后模型组予二甲基亚硝胺(Dimethylnitrosamine,DMN)诱导肝纤维化,4周后移植后模型组进一步分为移植+DMN组、移植+DMN+肝细胞生长因子(hepatocyte growth-promotting factors,pHGF)组与移植+DMN+FZHY组,pHGF与FZHY分别给药8周后,免疫荧光检测肝组织的GFP、白蛋白(Albumin,Alb)、α平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)及CD32的表达。[结果]移植8周末受体外周血涂片可见大量GFP;给药12周末,移植+DMN+FZHY组纤维间隔与肝实质区均可见GFP,实质区可见Alb,未见GFP+/Alb+,纤维间隔内可见GFP+/α-SMA+,但与移植+DMN组相比明显减少,窦状隙可见CD32+,可见明显GFP+/CD32+。[结论]在本实验建立的骨髓细胞移植后受体肝纤维化形成的体内微环境下,FZHY给药后,骨髓细胞有向肝实质区迁移的趋向,未能向肝细胞分化,可逆转其向肌成纤维细胞的分化失衡,可部分转分化为肝窦内皮细胞。[Objective]To explore the migration and differentiation of bone marrow mononuclear cells in liver fibrosis treated by Fuzheng Huayu recipe. [Methods]GFP（＋）marrow mononuclear cells from trans- genic murine donors were transplanted to wild type murine recipients and then dimetbylnitrosamine-treated liver fibrosis mice were conducted. Fuzheng Huayu recipe was administered and hepatocyte growth factor as positive control. [-Results^Microscopic examination of peripheral blood GFP（＋）cells confirmed success- ful transplantation. Immunofluorescenee showed the migration and differentiation. After Fuzheng Huayu recipe administration, （1）GFP emerged in fibrous septa and parenchyma but obviously less than that of dimethylnitrosamine treatment in fibrous septa and more in parenchyma; （2）GFP（＋）/albumin （＋） e- merged in parenchyma which was the same in dimethylnitrosamine treatment mice; （3）GFP （＋）/a-actin （＋） emerged in fibrous septa but obviously less than that of dimethylnitrosamine treatment;（4）GFP（ ＋ ）/ CD32 （＋） emerged in perisinusoidal space which was little in dimethylnitrosamine treatment mice, EConelu- sion^In this post-transplantation model of liver fibrosis, marrow mononuclear cells tend to migrate to fi- brous septa and differentiate to myofibroblasts. Fuzheng Huayu recipe tend to induce migration of marrow mononuelear cells to parenchyma, antagonize myofibroblasts differentiation and transdifferentiate to sinu- soida[ endothelial ceils.

关 键 词：细胞移植 骨髓 肝纤维化 扶正化瘀方 

分 类 号：R617[医药卫生—外科学] R242[医药卫生—临床医学]