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转染正义血管内皮细胞生长因子cDNA对大鼠肺泡巨噬细胞趋化蛋白1表达的影响 被引量:2

Effects of sense vascular endothelial growth factor cDNA transfection on mononuclear chemotaxis protein-1 expression in rat pulmonary microvessel endothelial cells
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摘要 目的探讨博莱霉素(BLM)致大鼠肺微血管内皮细胞紧密连接变化特征以及血管内皮细胞生长因子(VEGF)对肺微血管内细胞中巨噬细胞趋化蛋白1(MCP-1)mRNA表达的影响。方法健康SD大鼠按随机数字表法随机分为对照组和实验组。实验组大鼠制作BLM损伤肺纤维化模型,分别在第3、7、14以及28天行硝酸镧灌注后,制作肺组织病理标本,透射电镜观察血管内皮细胞(EC)紧密连接及镧颗粒分布。组织块培养法行大鼠肺微血管内皮细胞体外培养。体外培养的大鼠肺微血管内细胞中转染正义VEGF cDNA,采用逆转录-聚合酶链反应(RT-PCR)法检测MCP-1 mRNA的表达。结果对照组EC结构完整,基底膜呈连续线状。EC间连接紧密,镧盐颗粒未见通过EC间的紧密连接。实验组不同时间处理的大鼠均可见EC连接间隙增宽,并有高密度的镧颗粒在细胞连接间隙中线状沉淀,其中以第3天为著,分布于血管周围的内皮下区域,大部分通过基底膜到达细胞外间隙。与空白对照组比较,转染正义VEGF cDNA组肺微血管内皮细胞MCP-1 mRNA表达显著增加(P<0.05),空白对照组为0.36±0.06,转染组为1.21±0.22。结论BLM损伤肺微血管内皮细胞间紧密连接呈持续开放状态和MCP-1持续高表达,成为特异性定向诱导炎性细胞渗出和游走到组织间的病理基础,而炎性细胞持续分泌的细胞因子成为启动成纤维细胞过度增殖、诱发肺纤维化的重要因素之一。 Objective To study the transformation characteristics of tight junction of microvessel endothelial cells in bleomycin (BLM) induced pulmonary fibrosis (PF), and the effects of vascular endothelial growth factor ( VEGF ) on mononuclear chemotaxis protein-1 ( MCP-1 ) mRNA expression in pulmonary microvessel endothelial cells (EC). Methods Forty healthy rats were equally divided into a control and an experimental group in random. In the experimental group, PF were induced by BLM application. In each group, 10 rats were instilled by lanthanum sal at 3,7, 14 and 28 d after BLM application, and lung samples were made and observed by transmission electron microscopy. The pulmonary microvessel EC of the other 10 rats in each group were preserved by tissue culture methods at the same time, and the cells were transfected with sense VEGF eDNA, and then MCP-1 mRNA expression was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) technique. Results Blood vessel endothelial cells of the control group were intact. The basement membrane was shown as a continuous line. Granules of lanthanum sal did not cross the tight junction of endothelial cells. The width of the junction gap in rats of the experimental group treated at different times was increased and lanthanum particles of high density were seen in the gap junction, particularly on day 3, and were distributed in the area of subendothelium. The MCP-1 mRNA expression in VEGF transfected microvessel EC was significantly higher than that of the control group (1.21±0.22vs0.36±0.06, P〈0.05 ). Conclusion In BLMinduced PF, the opening of the tight junction of EC, and the high expression of MCP-1 induce inflammatory cell infiltration and cytokine oversecretion, which in turn enhances proliferation of fibroblasts, one of the important factors underlying lung fibrosis.
出处 《中华结核和呼吸杂志》 CAS CSCD 北大核心 2006年第1期44-47,共4页 Chinese Journal of Tuberculosis and Respiratory Diseases
关键词 肺纤维化 内皮生长因子 内皮 血管 博莱霉素 Pulmonary fibrosis Endothelial growth factors Endothelium, vascular Bleomycin
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参考文献9

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