人胎盘间充质干细胞来源细胞外囊泡调节肠炎小鼠肠黏膜胶原的沉积  

Human placenta mesenchymal stem cells-derived extracellular vesicles regulate collagen deposition in intestinal mucosa of mice with colitis

作　　者：段丽芸 曹晓沧[1] Duan Liyun;Cao Xiaocang(Department of Gastroenterology,General Hospital,Tianjin Medical University,Tianjin 300052,China)

机构地区：[1]天津医科大学总医院消化内科,天津市300052

出　　处：《中国组织工程研究》2021年第7期1026-1031,共6页Chinese Journal of Tissue Engineering Research

摘　　要：背景:肠道纤维化是炎症性肠病的常见并发症,可导致肠道功能损害和肠梗阻。肠道纤维化发生主要与细胞外基质成分如胶原、纤连蛋白的沉积和降解失衡有关。有研究发现间充质干细胞通过旁分泌机制分泌可溶性生物活性物质如细胞外囊泡,具有显著的抗纤维化作用。目的:探讨人胎盘间充质干细胞来源细胞外囊泡对肠炎小鼠肠黏膜胶原沉积的影响。方法:将24只BALB/c小鼠随机分为假手术组、模型组、细胞外囊泡组,每组8只。除假手术组外,其余两组使用2,4,6-三硝基苯磺酸(TNBS)灌肠法诱导建立肠纤维化模型,每日1次,持续6周。实验第3周开始细胞外囊泡组尾静脉注射细胞外囊泡,模型组给予等体积PBS,每日1次,持续到第6周。实验第1-7周统计比较小鼠疾病活动度指数评分、结肠质量/长度比值以评价细胞外囊泡的治疗效果,取病变肠段进行组织学染色及Western blot、RT-PCR检测纤维化相关指标以评估肠纤维化程度。结果与结论:①与模型组相比,细胞外囊泡组小鼠疾病活动度指数评分明显降低,结肠质量/长度比值明显降低,结肠病理表现明显改善;②与模型组相比,细胞外囊泡组小鼠结肠黏膜胶原沉积明显减轻,Ⅰ型、Ⅲ胶原及转化生长因子β1蛋白表达均明显下降;③与模型组相比,细胞外囊泡组小鼠结肠组织中基质金属蛋白酶2及基质金属蛋白酶9表达水平均明显升高,而金属蛋白酶组织抑制因子1表达水平下降;④结果表明,人胎盘间充质干细胞来源细胞外囊泡可明显改善小鼠结肠损伤严重程度及减少肠炎小鼠肠黏膜胶原沉积。BACKGROUND:Intestinal fibrosis is a common complication in inflammatory bowel disease and leads to functional damage and intestinal obstruction.Intestinal fibrosis is mainly related to the imbalance of deposition and degradation of extracellular matrix components,such as collagens and fibronectins.Studies have found that mesenchymal stem cells secreted soluble bioactive substance such as extracellular vesicles via paracrine action,which exerted marked anti-fibrosis effect.OBJECTIVE:To investigate the effect of human placenta mesenchymal stem cells-derived extracellular vesicles on collagen deposition in mice with colitis.METHODS:Totally 24 BALB/c mice were randomly divided into sham operation group,model group and extracellular vesicles group,with 8 mice in each group.Except the sham operation group,the remaining mice of model group and extracellular vesicles group were treated with trinitro-benzene-sulfonic acid to induce intestinal fibrosis,once a day for 6 weeks.The mice in the extracellular vesicles group and model group were administered with extracellular vesicles and phosphate-buffered saline,respectively,at 3 weeks,once a day for 6 weeks.The therapeutic effect of extracellular vesicles was evaluated by disease active index score and the colon weight/length ratio at 1-7 weeks.Diseased intestinal segment was subjected to histological staining.Western blot assay and RT-PCR were used to measure fibrosis related indicators so as to evaluate the degree of intestinal fibrosis.RESULTS AND CONCLUSION:(1)Compared with the model group,disease active index score and the colon weight/length ratio were significantly reduced,and colonic pathology was significantly improved in the extracellular vesicles group.(2)Compared with the model group,collagen deposition in colon mucosa of mice was significantly reduced,and the expression of collagen I,collagen III and transforming growth factor-β1 decreased significantly in the extracellular vesicles group.(3)Compared with the model group,expression levels of matrix metalloprote

关 键 词：干细胞 人胎盘间充质干细胞 细胞外囊泡 炎症性肠病 肠纤维化 胶原 实验 鼠 

分 类 号：R459.9[医药卫生—治疗学] R394.2[医药卫生—临床医学]