STAT1反义寡核苷酸雾化吸入对肺纤维化大鼠肺组织STAT1、ICAM-1及PDGF-A表达的影响  

Effect of aerosolized STAT1 antisense oligonucleotides on the expressions of STAT1,ICAM-1,and PDGF-A in lung tissue of pulmonary fibrosis rats induced by bleomycin

作　　者：王文军[1] 郭燕妮[1] 朱晨[2] 曾鸣[3] 李晶[1] 范贤明[1] 

机构地区：[1]泸州医学院附属医院呼吸内科,泸州646000 [2]四川省攀枝花市中心医院呼吸内科,攀枝花617000 [3]重庆市第二人民医院呼吸内科,重庆402160

出　　处：《中国免疫学杂志》2009年第8期736-741,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金资助项目(30570814);四川省教育厅资助项目(05011)资助项目

摘　　要：目的:观察信号转导子与转录活化子1(STAT1)反义寡核苷酸(ASON)雾化吸入对博莱霉素(BLM)致肺纤维化大鼠肺组织STAT1、细胞粘附分子-1(ICAM-1)和血小板衍生生长因子(PDGF)表达的影响。方法:取Wistar大鼠45只,随机分成生理盐水(NS)组、BLM组和ASON组,NS组气管内灌注NS,BLM组和ASON组气管内灌注BLM,随后NS组和BLM组雾化吸入NS,ASON组雾化吸入STAT1ASON,隔天雾化一次,共4次,分别于雾化后第7天、第14天、第28天处死大鼠各5只,右肺行支气管肺泡灌洗(BAL)进行细胞分类、计数;左肺免疫组化法测定肺组织中STAT1、ICAM-1和PDGF-A蛋白的表达。结果:①与BLM组比较,ASON组各时间点肺泡炎和肺纤维化程度明显减轻(P<0.05)。②与NS组比较,BLM组、ASON组肺组织STAT1、ICAM-1和PDGF-A表达水平均显著升高(P<0.01)。BLM组第7天STATl、ICAM-1、PDGF-A在肺组织中表达水平显著升高,随后下降,第28天时仍高于NS组(P<0.05)。与BLM组比较,ASON组各时间点STAT1、ICAM-1和PDGF-A表达水平降低(P<0.05)。结论:STAT1ASON雾化吸入能减轻BLM致肺纤维化大鼠肺泡炎和肺纤维化,其机制可能与STAT1被抑制后,炎症细胞在肺部浸润减轻,致炎因子和致纤维化因子分泌减少有关。Objective：To investigate the effect of aemsolized antisense oligonucleotides（ASON） of signal transducer and activator of transcription 1 （STAT1） on the expressions of STAT1 ,intercellular adhesion molecule- 1 （ ICAM-1 ）and platelet derived growth factor A（ PDGF- A） in lung tissue of pulmonary fibrosis rats induced by bleomycin（BLM） .Methods：45 adult female Wistar rats were randomly divided into 3 groups：normal saline（NS）group, bleomycin（BLM） group and ASON group. BLM group and ASON group were intratracheally instilled with BLM while NS group was instilled with NS.NS group and BLM group were aerosolized with NS while ASON group was aerosolized with STAT1 ASON on day 0,2,4,6. Then the rats were killed on day 7,14,28. Cell counting and differentiation in the bronchoalveolar lavage fluid（＇BAFL） of right lung was figured out, and STATI, ICAM-1 and PDGF-A protein in the tissue of left lung were assessed by immunohistochemistry. Results：（1）Compared with those of BLM group, the scores of alveohtis and fibrosis in ASON group were remarkably meliorated. （2） Compared with NS group, STAT1, ICAM- 1 and PDGF-A protein in lung tissue in BLM group and ASON group were obviously higher. The expressions of STAT1, ICAM-1 and PDGF-A protein in hmg tissue in BLM group were the highest at day 7,then dropped in,but still elevated over NS group at day 28 （ P 〈 0.05）. Compared with those of BLM group, the expressions of STAT1, ICAM-1 and PDGF-A protein in lung tissue in ASON .group were lower（ P 〈 0.05）. Conclusion： Aerosolized STAT 1 ASON could abate the alveolitis and the fibrosis in BLM-induced pulmonary fibrosis rats, which might result from inhibition of STAT 1 ,reduction of the infiltration of inflammatory cells,and the decrease of ICAM-1 and PDGF-A in lung tissue.

关 键 词：肺纤维化 信号转导子与转录活化子1 细胞间粘附分子-1 血小板源性生长因子-A 反义寡核苷酸 

分 类 号：R563.1[医药卫生—呼吸系统]