论文部分内容阅读
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)致肺纤维化大鼠肺泡灌洗液(BALF)PDGF-BB(血小板衍生生长因子-BB)、TNF-α(肿瘤坏死因子-α)、TGF-β1(转化生长因子-β1)、IFN-γ(干扰素-γ)表达及肺组织Ⅰ、Ⅲ型胶原mRNA表达的影响。方法:取45只健康雌性Wistar大鼠随机分成ASON组、BLM组和生理盐水(NS)组各15只,气管内分别灌注BLM(ASON组、BLM组)和NS(NS组)复制肺纤维化模型和空白对照,ASON组于第0、2、4、6天雾化吸入STAT1ASON,BLM组和NS组雾化吸入NS,各组分别于第7、14、28天均处死动物5只。观察肺泡炎和肺纤维化改变;收集BALF测定PDGF-BB、TNF-α、IFN-γ、TGF-β1的水平;测定肺组织Ⅰ、Ⅲ型胶原mRNA表达。结果:ASON组第7、14、28天肺泡炎和肺纤维化程度明显低于同时间点BLM组(P<0.05)。BLM组各时间点BALF中PDGF-BB、TNF-α、TGF-β1表达水平较NS组升高(P<0.05),ASON组较BLM组各时间点均降低(P<0.05);BLM组BALF中IFN-γ表达水平各时间点均低于NS组(P<0.05),但ASON组各时间点均较BLM组高(P<0.05)。ASON组和BLM组第7、14、28天Ⅰ、Ⅲ型胶原mRNA表达高于NS组(P<0.05);ASON组第7、14、28天Ⅰ、Ⅲ型胶原mRNA的表达均较同时间点BLM组降低(P<0.05)。结论:STAT1ASON雾化吸入能够减轻BLM诱导的肺泡炎和肺纤维化程度,其机制可能与抑制BALF中TGF-β1、PDGF-BB、TNF-α的表达,抑制IFN-γ下降而减少肺组织胶原的沉积有关。
OBJECTIVE: To observe the effects of atomization of signal transducer and activator of transcription 1 (STAT1) antisense oligonucleotide (ASON) on the proliferation of pulmonary fibrosis rats BALP induced by bleomycin (BLM) BB, TNF-α, TGF-β1, IFN-γ (interferon-γ) expression and lung tissue type Ⅰ, Ⅲ collagen Effect of mRNA expression. Methods: Forty-five healthy female Wistar rats were randomly divided into ASON group, BLM group and NS group. Each group was injected with BLM (ASON group, BLM group) and NS group (NS group) Model and blank control, inhaled STAT1ASON on day 0, day 2, day 4, and day 6, group NS on inhalation NS, group 5 were sacrificed on days 7, 14 and 28 respectively. The changes of alveolitis and pulmonary fibrosis were observed. The levels of PDGF-BB, TNF-α, IFN-γ and TGF-β1 were measured by BALF. The mRNA expression of type Ⅰ and type Ⅲ collagen in lung tissue was measured. Results: On the 7th, 14th and 28th days in ASON group, the degree of alveolitis and pulmonary fibrosis were significantly lower than those in BLM group (P <0.05). The expression of PDGF-BB, TNF-α and TGF-β1 in BALF at each time point in BLM group were significantly higher than those in NS group (P <0.05), while in ASON group were lower than those in BLM group at each time point (P <0.05), but the expression of IFN-γ was lower in ASON group than in BLM group at each time point (P <0.05). The expression of type I and type III collagen mRNA in ASON group and BLM group was higher than that in NS group on the 7th, 14th and 28th day (P <0.05) Point BLM group decreased (P <0.05). CONCLUSIONS: Inhaled inhaled STAT1ASON can attenuate the BLM-induced alveolitis and pulmonary fibrosis, which may be related to the inhibition of the expression of TGF-β1, PDGF-BB and TNF-α in BALF and the decrease of IFN-γ in BALF Deposition related.