雾化 STAT1 反义寡脱氧核苷酸对大鼠肺纤维化的影响。
The effects of aerosolized STAT1 antisense oligodeoxynucleotides on rat pulmonary fibrosis.
作者信息
Wang Wen Jun, Liao Bin, Zeng Ming, Zhu Chen, Fan Xian Ming
机构信息
The Department of Respiratory Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, China.
出版信息
Cell Mol Immunol. 2009 Feb;6(1):51-9. doi: 10.1038/cmi.2009.7.
Previous study showed that aerosolized signal transducer and activator of transcription-1 (STAT1) antisense oligodeoxynucleotide (ASON) inhibited the expression of STAT1 and ICAM-1 mRNA and protein in alveolar macrophages (AMs) and decreased the concentrations of TGF-beta, PDGF and TNF-alpha in bronchioalveolar lavage fluid (BALF) in bleomycin (BLM)-induced rat pulmonary fibrosis. Administration of STAT1 ASON ameliorated alveolitis in rat pulmonary fibrosis. However, further investigations are needed to determine whether there is an effect from administration of STAT1 ASON on fibrosis. This study investigated the effect of aerosolized STAT1 ASON on the expressions of inflammatory mediators, hydroxyproline and type I and type III collagen mRNA in BLM-induced rat pulmonary fibrosis. The results showed that STAT1 ASON applied by aerosolization could ameliorate alveolitis and fibrosis, inhibit the expressions of inflammatory mediators, decrease the content of hydroxyproline, and suppress the expressions of type I and type III collagen mRNA in lung tissue in BLM-induced rat pulmonary fibrosis. These results suggest that aerosolized STAT1 ASON might be considered as a promising new strategy in the treatment of pulmonary fibrosis.
先前的研究表明，雾化的信号转导和转录激活因子1（STAT1）反义寡脱氧核苷酸（ASON）可抑制肺泡巨噬细胞（AM）中STAT1和细胞间黏附分子-1（ICAM-1）的mRNA及蛋白表达，并降低博来霉素（BLM）诱导的大鼠肺纤维化模型支气管肺泡灌洗液（BALF）中转化生长因子-β（TGF-β）、血小板衍生生长因子（PDGF）和肿瘤坏死因子-α（TNF-α）的浓度。给予STAT1 ASON可改善大鼠肺纤维化中的肺泡炎。然而，仍需进一步研究以确定给予STAT1 ASON是否对纤维化有影响。本研究探讨了雾化STAT1 ASON对BLM诱导的大鼠肺纤维化中炎症介质、羟脯氨酸以及Ⅰ型和Ⅲ型胶原mRNA表达的影响。结果表明，雾化给予STAT1 ASON可改善肺泡炎和纤维化，抑制炎症介质的表达，降低羟脯氨酸含量，并抑制BLM诱导的大鼠肺纤维化模型肺组织中Ⅰ型和Ⅲ型胶原mRNA的表达。这些结果提示，雾化STAT1 ASON可能是治疗肺纤维化的一种有前景的新策略。
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