脂肪来源间充质干细胞治疗克罗恩病的实验研究  

Experimental study of adipose-derived mesenchymal stem cells in the treatment of Crohn′s disease

作　　者：谢明颢 何晓生[1] 朱金玲[1] 何真[1] 何小文[1] 兰平[1] 练磊[1] 

机构地区：[1]中山大学附属第六医院结直肠外科,广州510655

出　　处：《中华胃肠外科杂志》2015年第1期58-64,共7页Chinese Journal of Gastrointestinal Surgery

基　　金：国家自然科学基金（81200332）;广东省教育厅基金（2012LYM_0005）;中山大学青年教师培育项目（11ykpy45）

摘　　要：目的：探讨脂肪来源间充质干细胞（ADMSC）在克罗恩病（CD）治疗中的作用及可能的作用机制。方法采用三硝基苯磺酸（TNBS）法建立CD小鼠动物模型。将75只6～8周龄SPF级雌性BALB／c小鼠，随机分成3组，包括对照组（乙醇溶液灌肠加PBS腹腔注射）、TNBS组（TNBS灌肠加PBS腹腔注射）和ADMSC组（TNBS灌肠加ADMSC腹腔注射），每组25只。通过免疫组织化学染色和实时定量 PCR等方法检测组织炎性细胞因子的水平，并记录各组小鼠生存曲线。结果 ADMSC组较TNBS组病变程度明显减轻，生存率明显增加（60％比30％，P＜0．05）。ADMSC组促炎因子坏死因子α（TNF-α）、白介素12（IL-12）及血管内皮生长因子（VEGF）的表达显著低于TNBS组，而抑炎因子IL-10的表达显著增加（均P＜0．05）。结论 ADMSC可能通过下调促炎因子TNF-α、IL-12和VEGF的表达和上调抑炎因子IL-10的表达，有效修复结肠炎性损伤，有望用于CD的临床治疗。Objective To explore the efficacy of adipose-derived mesenchymal stem cells （ADMSCs） in a murine model of inflammatory bowel disease, and its potential mechanism. Methods Murine colitis mouse model of Crohn′s disease （CD） was created by trinitrobenzene sulfonic acid （TNBS）-induced colitis. Seventy-five 6-8 weeks female BALB/c mice were randomly divided into 3 groups： control group, TNBS group and ADMSC group. To verify the therapeutic effect of ADMSC, real-time PCR and immunohistochemical staining were performed to measure inflammatory cytokines levels in colon tissues. The 10-day survival statuses were recorded after the infusion of ADMSCs. Results Intraperitoneal injection of ADMSCs alleviated the clinical and histopathologic severity of intestinal inflammation, and increased survival（60% vs. 30%, P〈0.05） in the TNBS-induced mouse model of CD. Compared with TNBS group, proinflammatory cytokines, including TNF-α, IL-12 and VEGF of ADMSC group were significantly reduced, with significant increase of IL-10 expression. Conclusion ADMSCs can effectively repair the injury of colonitis through down-regulation of proinflammatory cytokines TNF-α, IL-12 and VEGF expression, and up-regulation of anti-inflammatory cytokine IL-10 expression, which may be a potential new alternative of cell-based therapy for CD.

关 键 词：脂肪间充质干细胞 克罗恩病 炎性因子 动物模型 小鼠 

分 类 号：R574.62[医药卫生—消化系统]