首页|脐带间充质干细胞对新生小鼠坏死性小肠结肠炎的保护作用

脐带间充质干细胞对新生小鼠坏死性小肠结肠炎的保护作用

Protective effects of umbilical cord mesenchymal stem cells on necrotizing enterocolitis in neonatal mice

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目的 探讨脐带间充质干细胞(umbilical cord mesenchymal stem cells,UC-MSCs)对坏死性小肠结肠炎(necro-tizing enterocolitis,NEC)小鼠模型肠组织的保护作用及可能的分子机制.方法 选取新生C57BL/6小鼠,采用高渗配方喂食、缺氧和冷刺激的方法,构建NEC小鼠模型,随机分为对照(母乳喂养)组、坏死性小肠结肠炎(NEC+PBS)组和间充质干细胞治疗(NEC+MSC)组,每组10只.UC-MSCs干预后,进行肠道宏观评估及HE染色观察肠组织病理形态学变化,免疫荧光染色检测上皮细胞增殖标志物KI-67和中性粒细胞浸润标记物髓过氧化物酶(myeloperox-idase,MPO)的表达;实时荧光定量PCR检测肠干细胞标记物富含亮氨酸的G蛋白偶联受体5(leucine-rich repeat containing G protein-coupled receptor 5,Lgr5)、炎症指标白介素 6(interleukin 6,IL-6)和肿瘤坏死因子(tumor necrosis factor,TNF-α)的mRNA表达.结果 UC-MSCs经腹腔注射给药后,NEC发生率由50%降低为20%(P<0.05);肠道损伤、小肠宏观学评分、组织病理学评分均低于NEC+PBS组,差异均有统计学意义(P=0.048 0和0.024 3,P均<0.05);肠道上皮细胞增殖标记物KI-67阳性细胞数量及肠道干细胞标记物Lgr5基因表达量较NEC+PBS组均增加,差异均有统计学意义(P=0.012 9、0.030 4,P均<0.05);肠道中性粒细胞浸润指标MPO、炎症指标IL-6和TNF-α较NEC+PBS组均降低,差异均有统计学意义(P=0.020 1、0.000 5和0.001 5,P均<0.05).结论 UC-MSCs可通过增加肠道上皮细胞增殖、恢复肠道干细胞活性和减少炎症因子来减轻NEC小鼠肠道损伤,具有较好的保护作用.
Objective To investigate the molecular mechanism and protective effect of umbilical cord mesenchymal stem cells(umbilical cord mesenchymal stem cells,UC-MSCs)on necrotizing enterocolitis(necrotizing enterocolitis,NEC)in neonatal mice.Methods Neonatal C57BL/6 mice were selected to develop NEC mouse model by using hypertonic formula feeding,hypoxia and cold stimulation.30 mice were randomly divided into three groups(10 mice in each group):control group(breast feeding),necrotizing enterocolitis group(NEC+PBS)and mesenchymal stem cell therapy group(NEC+MSC).After treatment with UC-MSCs,the pathomorphological changes in intestine were evaluated by HE staining.The ex-pression of KI-67,a marker of epithelial cell proliferation,and myeloperoxidase(MPO),a marker of neutrophil infiltration,were detected by immunofluorescence staining;and the mRNA expression of leucine-rich repeat containing G protein-cou-pled receptor 5(Lgr5),interleukin 6(IL-6)and tumor necrosis factor(TNF-α)were detected by real-time fluorescence quantitative PCR.Results After UC-MSCs administration by intraperitoneal injection,the incidence of NEC decreased from 50%to 20%(P<0.05);the intestinal injury,macroscopic score and histopathological score were lower than the control group,(P=0.048 0 and 0.024 3,P<0.05).The number of KI-67 positive cells and Lgr5 gene expression increased significantly compared with the control group(P=0.012 9 and 0.030 4,P<0.05);MPO,IL-6 and TNF-α were significantly reduced compared with the control group(P=0.020 1,0.000 5 and 0.001 5,P<0.05).Conclusion UC-MSCs can reduce intesti-nal injury by promoting the proliferation of intestinal epithelial cells,modulating the activities of intestinal stem cells and re-ducing inflammation in NEC mice.

Umbilical cord mesenchymal stem cellsNecrotizing enterocolitisIntestineProtection

杨柯、王薇、赵强、蔺莉

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甘肃省中心医院血液内科,甘肃兰州 730070

甘肃省中心医院内镜中心二部,甘肃兰州 730070

脐带间充质干细胞 坏死性小肠结肠炎 肠道 保护作用

甘肃省自然科学基金甘肃省自然科学基金兰州市科技计划项目兰州市科技计划项目

2022JR5RA7292021JR7RA0132022-3-172022-5-91

2024

微生物学免疫学进展
中华预防医学会 兰州生物制品研究所

微生物学免疫学进展

CSTPCD
影响因子:0.5
ISSN:1005-5673
年,卷(期):2024.52(1)
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