骨髓间充质样干细胞和骨髓单个核细胞影响博莱霉素诱导肺纤维化的比较  

Effect of bone marrow-derived mesenchymal-like stem cells versus bone marrow-derived mononuclear cells on bleomycin-induced pulmonary fibrosis

作　　者：陈娟[1] 刘薇薇[2] 刘移民[2] 李素梅[1] 余卫[2] 陈嘉榆[2] 张成[2] 林琛莅[1] 唐丽娟[1] 方茅[1] 钟雪云[1] 

机构地区：[1]暨南大学医学院病理学教研室,广东省广州市510632 [2]广东省广州市第十二人民医院,广东省广州市510632

出　　处：《中国组织工程研究与临床康复》2010年第36期6672-6676,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：广州市医药卫生科技项目(编号:2008-ZDi-04),项目名称:Smad7和HGF基因在矽肺纤维化的作用及靶向治疗的研究~~

摘　　要：背景:有报道指出,骨髓间充质样干细胞和骨髓单个核细胞在多种疾病中被证明有疗效,骨髓间充质样干细胞在肺纤维化模型中也有应用。目的:比较骨髓间充质样干细胞和骨髓单个核细胞对博莱霉素A5所致大鼠肺泡炎和早期纤维化的治疗作用。方法:收集Wistar雄性幼鼠的骨髓间充质样干细胞、骨髓单个核细胞并分别进行DAPI标记。21只Wistar雌性大鼠气管内注入博莱霉素A5制作肺损伤模型,随机均分为骨髓间充质样干细胞治疗组、骨髓单个核细胞治疗组和模型组。造模后第7天处死大鼠,取肺组织病理切片观察炎症和纤维化情况;荧光显微镜下检测DAPI标记细胞;ELISA法检测肺组织匀浆羟脯氨酸和肿瘤坏死因子的含量。结果与结论:①在骨髓间充质样干细胞治疗组、骨髓单个核细胞治疗组肺组织冰冻切片中均见到DAPI标记的外源细胞。②模型组肺泡炎最严重,骨髓间充质样干细胞治疗组肺泡炎最轻,各组比较,差异有显著性意义(P<0.05)。③模型组肺组织匀浆中羟脯氨酸和肿瘤坏死因子α含量最多,骨髓间充质样干细胞治疗最少,各组比较差异有显著性意义(P<0.05)。提示骨髓间充质样干细胞和骨髓单个核细胞均可定植于损伤肺组织,并能有效阻止博莱霉素A5诱导的大鼠肺泡炎和早期纤维化,前者作用更为显著。BACKGROUND：Previous studies demonstrated that many diseases can be effectively treated by using both bone marrow-derived mesenchymal-like stem cells （BM-MSCs） and bone marrow-derived mononuclear cells （BM-MNCs）.BM-MSCs also have been used in lung fibrosis models.OBJECⅡVE：To compare the curative effect of BM-MSCs and BM-MNCs for treating bleomycin A5-induced alveolitis and early fibrosis.METHODS：BM-MSCs and BM-MNCs from Wistar male young rats were cultured and marked with 4, 6-diamidino-2-phenylindole （DAPI）.A total of 21 female Wistar rats were intratracheally injected with bleomycin A5 to establish pulmonary fibrosis models.The rats were randomly divided into BM-MSCs group, BM-MNCs group and model group.The rats were sacrificed on day 7 following model induction.Pathological sections of pulmonary tissues were obtained to observe inflammation and fibrosis.Fluorocyte marked with DAPI was detected by fluorescence microscopy.The levels of hydroxyproline and tumor necrosis factors-α （TNF-α） were measured by enzyme linked immunosorbent assay （ELISA）.RESULTS AND CONCLUSION：① In BM-MSCs group and BM-MNCs group, BM-MSCs and BM-MNCs marked with DAPI were detected in lung frozen section.②Pulmonary alveolitis was most serious in model group, pulmonary alveolitis and fibrosis in BM-MNCs group was more serious than BM-MSCs group, and significant differences were detected among groups （P〈0.05）.③ Hydroxyproline and TNF-α levels were highest in model group, and lowest in the BM-MSCs group, and significant differences were detected among groups （P〈0.05）.Results suggest that both BM-MSCs and BM-MNCs can be planted in the impaired lung tissue, and effectively prevent the development of bleomycin-induced pulmonary alveolitis and early fibrosis.The curative effect of BM-MSCs is better than that of BM-MNCs.

关 键 词：骨髓单个核细胞 骨髓间充质样干细胞 细胞移植 肺纤维化 肿瘤坏死因子Α 

分 类 号：R394.2[医药卫生—医学遗传学]