骨髓间充质干细胞治疗慢性阻塞性肺疾病中的Wnt/β-catenin信号通路  

Wnt/beta-catenin signaling pathway in the treatment of chronic obstructive pulmonary disease with bone marrow mesenchymal stem cells

作　　者：钟玉兰 周湘乡 淦鑫[2] Zhong Yulan;Zhou Xiangxiang;Gan Xin(Jiangxi Provincial Chest Hospital,Nanchang 330006,Jiangxi Province,China;Department of Respiratory and Critical Care Medicine,First Affiliated Hospital of Nanchang University,Nanchang 330006,Jiangxi Province,China)

机构地区：[1]江西省胸科医院,江西省南昌市330006 [2]南昌大学第一附属医院呼吸与危重症医学科,江西省南昌市330006

出　　处：《中国组织工程研究》2022年第13期1979-1984,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(81660009,81260004),项目负责人:淦鑫;江西省自然科学基金(20192BAB215002),项目参与人:淦鑫

摘　　要：背景:骨髓间充质干细胞(bone marrow-derived mesenchymal stem cells,BMSCs)治疗呼吸系统疾病具有广泛的应用前景,近年来研究显示Wnt/β-catenin信号通路在调控BMSCs定向分化及促进旁分泌方面起重要作用。目的:探讨激活Wnt/β-catenin信号通路对BMSCs移植治疗慢性阻塞性肺疾病的影响。方法:采用全骨髓贴壁法提取大鼠BMSCs,用Wnt3a慢病毒转染大鼠BMSCs。采用气管内注入脂多糖联合烟熏法构建慢性阻塞性肺疾病大鼠模型,造模完成后经尾静脉植入BMSCs、GFP-BMSCs、Wnt3a-BMSCs,模型组和正常对照组经尾静脉注入PBS,分别在第7,14,28天处死各组大鼠,苏木精-伊红染色观察肺组织病理改变,ELISA检测动脉血中白细胞介素10、肿瘤坏死因子α水平。结果与结论:①苏木精-伊红染色病理结果显示:3个BMSCs移植组较模型组病理改变明显改善,其中Wnt3a-BMSCs组改善相对明显;②在相同时间点,3个BMSCs移植组动脉血中肿瘤坏死因子α水平低于模型组(均P<0.05),其中BMSCs组、GFP-BMSCs组差别不大,但Wnt3a-BMSCs组明显低于其他两组(P<0.05);3个BMSCs移植组动脉血中白细胞介素10水平高于模型组(均P<0.05),其中BMSCs组、GFP-BMSCs组差别不大,但Wnt3a-BMSCs组明显高于较其他两组(P<0.05);③结果表明,过表达Wnt3a(Wnt/β-catenin信号通路激活)的BMSCs植入慢性阻塞性肺疾病大鼠体内,可显著改善肺组织病理形态,提高抗炎因子白细胞介素10水平,降低促炎因子肿瘤坏死因子α水平,增强BMSCs的抗炎作用。BACKGROUND:Bone marrow mesenchymal stem cells(BMSCs)have a wide application prospect for the treatment of respiratory diseases.In recent years,studies have shown that the Wnt/β-catenin signaling pathway plays an important role in regulating the directional differentiation of BMSCs and promoting paracrine function.OBJECTIVE:To investigate the effect of Wnt/β-catenin signaling pathway activation on chronic obstructive pulmonary disease after transplantation with BMSCs.METHODS:Whole bone marrow adherence method was used to extract rat BMSCs.Rat BMSCs were infected with Wnt3a lentivirus.The chronic obstructive pulmonary disease rat model was constructed by intratracheal infusion of lipopolysaccharide combined with smoking method.After model establishment,BMSCs,GFP-BMSCs,and Wnt3a-BMSCs were implanted through the tail vein.PBS was injected through the tail vein in the model and normal control groups.The rats in each group were sacrificed at 7,14,and 28 days.The pathological changes of rat lung tissue were observed by hematoxylin-eosin staining.The levels of interleukin-10 and tumor necrosis factor alpha in arterial blood were detected by ELISA.RESULTS AND CONCLUSION:(1)The pathological results of hematoxylin-eosin staining showed that the pathological changes of the three BMSCs transplantation groups were significantly improved compared with the model group,and the Wnt3a-BMSCs group improved significantly.(2)At the same time point,the arterial blood tumor necrosis factor alpha level was lower in the three BMSCs transplantation groups than that in the model group(all P<0.05),and there was little difference between the BMSCs group and the GFP-BMSCs group.However,the level in the Wnt3a-BMSCs group was relatively lower than that in the other two groups(P<0.05).Arterial blood interleukin-10 level was higher in the three BMSCs transplantation groups than that in the model group(all P<0.05),among which there was little difference between the BMSCs group and the GFP-BMSCs group.However,the level in the Wnt3a-BMSCs group was

关 键 词：干细胞 骨髓间充质干细胞 慢性阻塞性肺疾病 WNT3A Wnt/ß-catenin信号通路 白细胞介素10 肿瘤坏死因子α 

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