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目的重组尿激酶型纤溶酶原激活物(ru-PA)不同用药方案对栓塞处肥大细胞(MC)分布的影响及意义。方法通过颈外静脉注入125碘(125I)-标记人纤维蛋白原的大鼠加热血凝块,建立大鼠肺血栓栓塞症(PTE)模型。随机将30只大鼠分成两大组:对照组(n=10);溶栓组:再分为多次用药组及单次用药组(n=10)。定时处死大鼠,取血、肺及心脏,测量每分钟γ放射性(cpm)。以10%甲醛固定肺组织,制成组织切片,行苏木精-伊红(HE)染色观察血栓的形态,Masson染色观察栓塞血管的胶原纤维分布,甲苯胺蓝染色观察血管栓塞处肥大细胞分布。结果栓塞血管断面可见MC聚集现象,ru-PA多次用药组栓塞处MC计数及溶栓率明显高于单次用药组及对照组,单次用药组明显高于对照组(均P<0.01)。经线性相关性分析,多次用药组及单次用药组血管栓塞处MC计数与溶栓率均呈显著正相关(r=0.766及0.743;P=0.010及0.014)。结论PTE血管栓塞处有MC聚集现象;维持ru-PA在血中一定浓度的持续时间,促进MC聚集于栓塞血管部位,该时间越长,趋化MC向栓塞处迁移、聚集越多,并加强ru-PA的溶栓效果。
OBJECTIVE: To study the effect of different regimens of recombinant human urokinase-type plasminogen activator (ru-PA) on the distribution of mast cells (MCs) at embolic sites and its significance. Methods Pulmonary thromboembolism (PTE) rat model was established by heating clot with 125 iodine-labeled human fibrinogen through external jugular vein. Thirty rats were randomly divided into two groups: control group (n = 10); thrombolytic group: divided into multiple drug groups and single drug group (n = 10). Rats were sacrificed at regular intervals, blood, lungs and heart were taken and γ-radioactivity (cpm) was measured. The lung tissues were fixed with 10% formalin to make tissue sections. The thrombus morphology was observed by hematoxylin-eosin (HE) staining. The distribution of collagen fibers in the embolized vessels was observed by Masson staining. The distribution of mast cells in the embolization vessel was observed by toluidine blue staining . Results MC aggregation was observed in the embolized blood vessels. The counts of embolization and the rate of thrombolysis in ru-PA multi-drug group were significantly higher than those in single-drug group and control group, and were significantly higher in single-drug group than those in control group (all P <0.01) . According to the linear correlation analysis, there was a significant positive correlation between MC count and thrombolysis rate in multiple drug administration group and single drug administration group (r = 0.766 and 0.743; P = 0.010 and 0.014, respectively). Conclusions There is aggregation of MC in the embolization of PTE, maintaining the duration of ru-PA in the blood and promoting the accumulation of MC in the embolized blood vessels. The longer the time, the more chemotactic MC migrates to the embolism, the more aggregation and enhancement ru-PA thrombolytic effect.