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目的:探讨肺泡巨噬细胞(AM)中STAT1(signal transducersand activators of transcription 1)的活化在大鼠肺间质纤维化中的作用。方法:50只健康雌性Wistar大鼠随机分成博莱霉素(BLM)组和生理盐水(NS)组各25只,气管内分别灌注BLM和NS。用Western-blot法测定AM中STAT1活化的动态变化;用免疫组化染色法测定AM的ICAM-1(intercellular adhesionmolecule-1)的表达。结果:NS组中的AM内只有少许STAT1活化,气管内灌注BLM后1d,AM中STAT1的活化即开始显著增高,于第7天达高峰,以后逐渐下降,但28 d后仍高于NS组(P<0.05)。NS与BLM组的AM中表达ICAM-1的细胞数增高的模式,与AM中STAT1活化的模式相同。AM中STAT1活化的程度与AM中ICAM-1的表达呈正相关(r=0.913,P<0.01),而后者又与肺组织炎症的积分呈正相关(r=0.947,P<0.01)。结论:实验性肺间质纤维化大鼠AM中存在STAT1的异常活化,并参与了肺泡炎和肺纤维化的形成。
AIM: To investigate the role of signal transducers and activators of transcription 1 in pulmonary interstitial fibrosis in rat alveolar macrophages (AM). Methods: Fifty healthy female Wistar rats were randomly divided into BLM group (n = 25) and NS group (n = 25). BLM and NS were perfused intratracheally. The dynamic changes of STAT1 activation in AM were detected by Western-blot and the expression of ICAM-1 (intercellular adhesionmolecule-1) in AM was detected by immunohistochemical staining. RESULTS: Only STAT1 was activated in AM group. Activation of STAT1 began to increase at 1 day after intratracheal instillation of BLM, peaked on the 7th day, and then decreased gradually after 28 days, but still higher than that in NS group (P <0.05). The pattern of increased ICAM-1 expression in AMs in NS and BLM groups was identical to the pattern of STAT1 activation in AMs. The level of STAT1 activation in AM was positively correlated with the expression of ICAM-1 in AM (r = 0.913, P <0.01), while the latter was positively correlated with the score of lung inflammation (r = 0.947, P <0.01). Conclusion: The abnormal activation of STAT1 exists in experimental AM rats and is involved in the formation of alveolitis and pulmonary fibrosis.