结核性胸膜炎模型大鼠胸腔积液MMP-1和TIMP-1表达

Expression of MMP-1 and TIMP-1 in Pleural Effussion in Tuberculous Pleurisy Rats

目的探讨基质金属蛋白酶1(MMP-1)及其组织抑制物1(TIMP-1)在结核性胸膜炎胸腔积液不同阶段的作用。方法 Wistar雄性大鼠60只,将人型结核菌株H37Rv注入50只实验组大鼠右侧胸腔内,另10只对照组大鼠同侧胸腔注入纯化蛋白衍生物(PPD)原液,注入后第1、3、7、15、30天分批处死大鼠,解剖胸腔,记录胸腔积液量,观察两组大鼠胸腔、胸膜和肺组织大体及镜下病理变化,采用酶联免疫吸附试验(ELISA)法测定两组大鼠胸腔积液中MMP-1和TIMP-1浓度。结果对照组大鼠在注入第1天时胸腔积液量为1.3m L,不能进行MMP-1和TIMP-1有效常规检测,第3天后完全吸收。实验组大鼠15天内均有右侧胸腔积液,第1、3、7、15天胸腔积液量分别为(4.9±0.5)m L、(6.3±0.4)m L、(7.2±0.6)m L、(2.5±0.3)m L,第7天最多;胸腔积液中MMP-1和TIMP-1浓度分别为(9.54±0.97)ng/m L和(27.06±2.61)ng/m L、(15.62±1.30)ng/m L和(35.68±2.70)ng/m L、(29.78±1.97)ng/m L和(40.07±3.61)ng/m L、(35.12±2.13)ng/m L和(42.15±3.08)ng/m L,均呈逐渐升高趋势。结论结核性胸膜炎早期局部免疫反应以持续增强为主,MMP-1、TIMP-1在此过程中发挥作用。

Objective To investigate the effects of matrix metalloproteinase-1（MMP-1） and tissue inhibitors of met alloproteinase（TIMP-1） in the process of development of tuberculous pleurisy in rats. Methods Fifty male Wistar rats that were injected into the right pleural cavity with H37 Rv of mycobacterium tuberculosis, were set as the experimental group. Another 10 rats that were injected with 1 m L purified protein derivative（PPD） solution, served as control group. The rats were were killed in batches on Day 1, Day 3, Day 7, Day 15 and Day 30 after injection, then the chest were dissected to record the amount of pleural effusion and to observe the morphological and pathological changes of pleural and lung. MMP-1 and TIMP-1 concentrations in pleural effusion of each rat were measured by enzyme-linked immunosorbent assay（ELISA） method. Results The amount of pleural effusion in control group was 1.3m L on Day 1 after injection of PPD solution, which made control rats not eligible for routine; pleural effusion completely absorbed on Day 3. The rats of experimental group had pleural effusion in the right pleural cavity within the first 15 days and the amount of pleural effusion on Day 1, Day 3, Day 7 and Day 15 were as follows： 4.9 ±0.5m L,6.3±0.4m L, 7.2±0.6m L, 2.5±0.3m L, the maximum amount was on Day 7; the concentrations of MMP-1 and TIMP-1 in pleural effusion were as follows： 9.54±0.97ng/m L and 27.06±2.61ng/m L, 15.62±1.30ng/m L and 35.68±2.70ng/m L, 29.78±1.97ng/m L and 40.07±3.61ng/m L, 35.12±2.13ng/m L and 42.15±3.08ng/m L, both of which showed a gradually increasing trend. Conclusion The local immune response is increasing at early stage of tuberculous pleurisy. TIMP-1 and MMP-1 play a role in a series of processes, including the local inflammatory response, tissue necrosis and repair in the thoracic cavity.