中文摘要：

目的探讨上调miR-489是否对矽尘诱导的小鼠肺纤维化成熟期有一定治疗作用。方法雄性C57BL/6小鼠32只分为生理盐水组、矽尘组、矽尘＋miRNA对照组、矽尘＋miR-489组。每组8只。经气管一次灌注SiO2粉尘悬液的方法建立小鼠矽肺模型，并于染尘后第28、35、42和49天经尾静脉注射miRNA对照和miR-489 agomir，第56天收集肺组织，观察肺纤维化病理改变、胶原含量，检测肺组织miR-489、E-钙黏蛋白、α-平滑肌肌动蛋白（α-SMA）、波形蛋白、纤连蛋白及转化生长因子（TGF-β1）的水平。结果与矽尘＋miRNA对照组比较，矽尘＋miR-489组可显著上调肺组织中miR-489水平，差异有统计学意义（P〈0.05）。病理切片显示矽尘＋miR-489组肺组织炎症反应、肺泡结构破坏和纤维化结节形成出现减轻，矽尘＋miR-489组肺损伤的严重程度和分布范围肺纤维化评分均低于矽尘＋miRNA对照组，差异有统计学意义（P〈0.05）。与矽尘＋miRNA对照组比较，矽尘＋miR-489组肺组织中胶原沉积和羟脯氨酸含量降低，差异有统计学意义（P〈0.05）。与矽尘＋miRNA对照组比较，矽尘＋miR-489组肺组织α-SMA、波形蛋白、纤连蛋白、TGF-β1蛋白水平降低，而E-钙黏蛋白水平升高，差异有统计学意义（P〈0.05）。结论上调小鼠体内miR-489水平对矽尘诱导的肺纤维化发挥一定治疗作用，这可能与其降低TGF-β1的释放有关。

英文摘要：

ObjectiveTo explore the potential therapeutic role of miR-489 in silica-induced pulmonary fibrosis mouse models.Methods A total of 32 C57BL/6 male mice were randomly divided into four groups： saline, silica, silica plus miRNA control and silica plus miR-489 agomir （n=8 in each group） . The mice were instilled with silica particles suspended in saline or sterile saline intratracheally. Subsequently, miR-489 agomir or miRNA control was injected via the tail vein into each mouse at days 28, 35, 42 and 49, the miR-489 levels, histological examination, collagen deposition, fibrotic biomarkers （E-cadherin, α-SMA, Vimentin, Fibronectin） and transforming growth factor-β1 （TGF-β1） protein levels in mouse lung tissues were measured.ResultsmiR-489 levels in silica plus miR-489 group were significantly increased in lung tissues compared with silica plus miRNA control group （P〈0.05） . Histological examination showed attenuated inflammation, less severe fibrotic foci and less destruction of alveolar architecture in the silica plus miR-489 group. Additionally, both the severity and distribution of lung lesions were ameliorated in silica plus miR-489 group compared with the silica plus miRNA control group （P〈0.05） . The collagen deposition and hydroxyproline levels in silica plus miR-489 group were significantly decreased compared with the silica plus miRNA control group （P〈0.05） . These changes were supported by decreased protein levels of α-SMA, Vimentin, Fibronectin, TGF-β1 along with increased protein levels of E-cadherin in silica plus miR-489 group （P〈0.05） .ConclusionOur data indicate that the upregulation of miR-489 has potential therapeutic role in silica-induced pulmonary fibrosis in vivo, which may be associated with the depression of TGF-β1 release.