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目的研究尿激酶型纤溶酶原激活物(uPA)及其纤溶酶原抑制因子(PAI-1)在矽肺纤维化发病中的作用机制及其相互关系。方法 Wistar大鼠60只,分为染尘模型组(简称模型组)与对照组,分别30只。矽尘混悬液缓慢注入气管造模,对照组注入生理盐水。分别在5个时间点处死大鼠,取肺组织HE染色,观察病理变化。免疫组化方法检测肺组织中uPA、PAI-1、基质金属蛋白酶-9(MMP-9)、蛋白酶抑制剂-2(TIMP-2)蛋白的表达。免疫结果半定量判断参照免疫组化显色标准。结果 uPA、PAI-1在模型组均有较强阳性表达,与对照组比较,差异有统计学意义(P<0.01)。MMP-9阳性表达强度随时间延长逐渐增强,至第7天时达高峰,此后呈减弱趋势,TIMP-2染色明显增强并保持到第4周,与对照组比较,差异有统计学意义(P<0.05)。uPA、PAI-1、MMP-9、TIMP-2显色指数与对照组比较差异有统计学意义(P<0.05)。结论 uPA、PAI-1、MMP-9、TIMP-2四者表达均呈正相关,在矽肺纤维化中MMPs的升高可能与PAI-1的降低有关,矽肺的发展过程中可能存在uPA诱导的纤溶系统的活化与MMPs介导通路的交互作用网络。
Objective To investigate the mechanism and relationship of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in the pathogenesis of silicotic fibrosis. Methods Sixty Wistar rats were divided into two groups: model group (model group) and control group (n = 30). Silica suspension was slowly injected into the trachea model, the control group injected with saline. The rats were sacrificed at 5 time points, and the lungs were stained with HE to observe the pathological changes. The expressions of uPA, PAI-1, MMP-9 and TIMP-2 in lung tissue were detected by immunohistochemistry. Semi-quantitative evaluation of immune results with reference to immunohistochemical color standards. Results The expression of uPA and PAI-1 in the model group was stronger than that in the control group (P <0.01). The positive expression intensity of MMP-9 gradually increased with time, reaching its peak on the 7th day, then weakened, the TIMP-2 staining increased significantly and remained to the 4th week, the difference was statistically significant (P < 0.05). The color index of uPA, PAI-1, MMP-9 and TIMP-2 were significantly different from the control group (P <0.05). Conclusions The expression of uPA, PAI-1, MMP-9 and TIMP-2 are all positively correlated. The increase of MMPs in silicotic fibrosis may be related to the decrease of PAI-1. The development of silicosis may have uPA- The activation of the lysosomal system interacts with the MMPs-mediated pathway.