肾脏纤维化中转化生长因子β1对骨髓源巨噬细胞向肌成纤维细胞转化的调控机制  

The effect of transforming growth factor β1 in the transition of bone marrow-derived macrophages into myofibroblasts during renal fibrosis

作　　者：杨莹[1] 冯晓剑 刘新艳[1] 王利华[1] 郑国平[2] 

机构地区：[1]山西医科大学第二医院肾内科,太原030001 [2]山西医科大学生化教研室

出　　处：《中华内科杂志》2017年第8期610-613,共4页Chinese Journal of Internal Medicine

摘　　要：探究骨髓源细胞转化为肌成纤维细胞的主要细胞类型及转化生长因子β1（TGFβ1）参与调控其转化过程的机制.取绿色荧光蛋白标记C57小鼠骨髓移植于辐照清髓小鼠体内,经骨髓再造12周,制作单侧输尿管结扎（UUO）模型,简单随机法随机分为假手术组、UUO3d组、UUO5d组、UUO7d组、UUO7d＋ TGFβ1组,每组4只.流式检测骨髓源各型细胞的转化情况.结果显示,随UUO造模时间的延长,小鼠肾组织中GFP＋ CD14^＋ α-SMA＋细胞、GFP^＋CD44^＋CD105^＋α-SMA＋细胞、GFP^＋ F4/80^＋α-SMA＋细胞表达逐渐增多,其中UUO7d最多,GFP^＋ F4/80^＋α-SMA^＋细胞在3种细胞中所占比例最多,是主要的细胞类型.UUO7d^＋ TGFβ1组GFP^＋ F4/80^＋α.-SMA＋细胞表达水平高于假手术组和UUO7d组,提示TGFβ1促进骨髓源巨噬细胞转化为肌成纤维细胞.UUO7d^＋ TGFβ1组小鼠肾组织病理表现为肾小管和肾间质中胶原纤维明显增多,F4/80、胶原蛋白Ⅰ表达明显增多,α-SMA表达明显增多.骨髓源单核细胞、间充质干细胞、巨噬细胞均有转化为肌成纤维细胞的可能,其中骨髓源巨噬细胞是主要的转化细胞类型.TGFβ1促进骨髓源巨噬细胞向肌成纤维细胞转化,从而加重肾脏纤维化及肾功能恶化.To study which subgroup of bone marrow derived cells formed myofibroblasts and the mechanism that transforming growth factor β1 （TGFβ1） regulates the formation of bone marrow derived macrophages into myofibroblasts during renal fibrosis.Chimeric mice were generated by lethally irradiation of C57 mice followed by transfusion of green fluorescent protein （GFP） labeled bone marrow cells.Complete marrow reconstitution was developed until 12 weeks after transplantation.The mice were randomly divided into Sham operation group,unilateral ureteral obstruction （UUO） 3 days group,UUO5 days group,UUO7 days group and UUO7 with TGFβ1 treatment group.Each group had four mice.Flow cytometry was used to evaluate cell components.Compared with Sham operation group the proportions of GFP ^＋ CD14^＋ oα-smooth muscle actin（α-SMA） ^＋ cells,GFP ＋ CD44^＋ CD105^＋ α-SMA^＋ cells and GFP^＋ F4/80^＋ α-SMA^＋ cells in each UUO group were progressively increased and the transformation rate in UUO7 day group was the highest.The GFP^＋ F4/80 ^＋ α-SMA＋ cells accounted for the largest population.TGFβ1 promoted the transformation of bone marrow derived macrophages into myofibroblasts.Compared with Sham operation group or UUO7 day group,the proportion of GFP＋ F4/80＋ α-SMA＋ cells increased in UUO7 day TGFβ1 treatment group.Compared with Sham operation group （or UUO7 days group） the protein expressions of F4/80,oα-SMA,Collagen Ⅰ increased in UUO7 with TGFβ1 group.Bone marrow derived macrophages are considered as the main type of myofibroblast precursors during the development of renal fibrosis.TGFβ1 regulates the transformation of bone marrow-derived macrophages into myofibroblasts.This process contributes to progressive renal fibrosis and deterioration of renal function.

关 键 词：转化生长因子Β1 骨髓源巨噬细胞 肾脏纤维化 

分 类 号：R692[医药卫生—泌尿科学]