鼠骨髓间充质干细胞移植对溃疡性结肠炎大鼠结肠的修复作用研究  

Repair of colon in rats with ulcerative colitis by rat bone marrow mesenchymal stem cells transplantation

作　　者：高福来[1] 纪桂贤[1] 张利利[1] 李莉[1] 崔红梅[1] GAO Fulai;JI Guixian;ZHANG Lili;LI Li;CUI Hongmei(Qinhuang dao No. 1 Hospital, Qinhuangdao 066000, Hebei , China)

机构地区：[1]秦皇岛市第一医院,河北秦皇岛066000

出　　处：《西部医学》2018年第7期956-960,965,共6页Medical Journal of West China

基　　金：秦皇岛市科学技术局科研项目(201401A291)

摘　　要：目的探讨鼠骨髓间充质干细胞(BMSCs)移植对溃疡性结肠炎(UC)大鼠结肠的修复作用。方法体外培养雄性BALA/c大鼠BMSCs,选择75只雄性BALA/c大鼠,随机分为正常组、模型组,低、中、高浓度组各15只,用葡聚糖硫酸钠(DSS)诱导建立UC大鼠模型。正常组和模型组大鼠尾静脉注射0.4ml生理盐水,低、中、高浓度组大鼠采用尾静脉注射BMSCs悬液0.4ml,细胞浓度分别为0.5×106/ml、1×106/ml、2×106/ml。记录大鼠活动和体征,用疾病活动指数(DAI)进行评分,检测大鼠血清TNF-α(肿瘤杀伤因子-α)、IL-6(白介素6)、IL-8(白介素8)、D-LAC(D-乳酸)、DAO(二胺氧化酶)含量,将大鼠一部分结肠组织制作切片,镜下观察。另一部分制成组织匀浆,检测MPO(髓过氧化物酶)含量。结果经过移植后,低、中、高浓度组大鼠结肠充血水肿情况好于模型组,溃疡和糜烂减少,炎性细胞减少。模型组大鼠血清TNF-α、IL-6、IL-8含量明显高于正常组,差异有统计学意义(P<0.05);低、中、高浓度组TNF-α、IL-6、IL-8含量均低于模型组,且随着浓度的升高,各组TNF-α、IL-6、IL-8含量均降低,差异均有统计学意义(P<0.05);移植后第7d,模型组与低浓度组大鼠血清D-LAC、DAO、组织MPO含量高于其余组(P<0.05);移植后第21d,低、中、高浓度组大鼠血清D-LAC、DAO、组织MPO含量与正常组无差异(P>0.05);移植后第7、21d,各组DAI评分均下降,低、中、高浓度组低于模型组,且随着浓度的升高,DAI评分越低,差异均有统计学意义(P<0.05)。结论采用鼠骨髓间充质干细胞移植治疗溃疡性结肠炎大鼠,能够明显改善大鼠病情,可能是通过抑制炎症因子的分泌,从而减轻炎症反应,使肠道屏障功能恢复,但治疗的作用机制还需要进一步深入研究。Objective To study the effect of bone marrow mesenchymal stem cells transplantation on colon repair in rats with ulcerative colitis.Methods BMSCs male BALA/c rats were cultured in vitro.75 male BALA/c rats were randomly divided into normal group,model group,low,medium and high concentration group with 15 rats each.UC rat model was induced by dextran sulfate sodium.0.4 ml saline was injected into tail vein of rats in normal group and model group.Rats in low,medium and high concentration groups were injected BMSCs suspension with tail vein 0.4 ml,and the cell concentration was 0.5×10^6/ml,1×10^6/ml and 2×10^6/ml respectively.The activity of rats and signs recorded by disease activity index（DAI）score,serum TNF-α,IL-6,IL-8,D-LAC and DAO content.A section of colon tissue in rats was sliced and observed under microscope.The other part was made into tissue homogenates to detect MPO content.Results After transplantation,the congestion and edema of the colon in the lower,middle and high concentration groups were better than that in the model group,and the ulcer and erosion decreased,and the inflammatory cells decreased.The levels of serum TNF-α,IL-6 and IL-8 in the model group were significantly higher than that in the normal group（P〈0.05）.The concentrations of TNF-α,IL-6 and IL-8 in the low,middle and high concentration groups were lower than those in the model group,and with the increase of the concentration,the levels of TNF-α,IL-6 and IL-8 in the groups decreased（P〈0.05）.After transplantation,the content of serum D-LAC,DAO and tissue MPO in the model group and the low concentration group were higher than those in the other group after 7 d（P〈0.05）.The levels of serum D-LAC,DAO and tissue MPO in the rats of low,medium and high concentration groups after transplantation were not different from those in the normal group after 21 d（P〉0.05）.After transplantation seventh and 21 d,the DAI scores of all groups decreased,and the low,middle and high concentration groups were lower than the mode

关 键 词：骨髓间充质干细胞 溃疡性结肠炎 肠道屏障 炎症因子 移植 

分 类 号：R-33[医药卫生] R574.62