摘要目的 观察平阳霉素胸膜腔内注射后对外周血及胸腔积液中纤溶酶原激活剂抑制物1(PAI-1)、组织型纤维蛋白溶酶原活化剂(t-PA)及转化生长因子β_1(TGF-β_1)水平的影响,探讨胸膜腔内注射平阳霉素治疗恶性胸腔积液(MPE)的机制.方法 2008年2-9月对26例MPE患者胸膜腔内注射平阳霉素,检测注药前后外周血及胸腔积液中PAI-1、t-PA、TGF-β_1的水平及白细胞计数.1个月后根据WHO制定的统一标准评价疗效,其中完全缓解(胸腔积液完全消失并维持1个月以上)和部分缓解(胸腔积液减少50%以上)者归为有效组;胸腔积液减少后再次增加且30 d内需再次抽液者,归为无效组.结果 1个月后15例(15/26例)胸腔积液控制;注射平阳霉素后24 h外周血中自细胞计数[有效组为(9.2±2.0)×10~9/L,无效组为(9.4±3.8)×10~9/L]、中性粒细胞计数[有效组为(7.9±2.1)×10~9/L,无效组为(8.1±3.3)×10~9/L]与注药前外周血白细胞计数[有效组为(6.6±1.4)×10~9/L,无效组为(5.6±0.9)×10~9/L]和中性粒细胞计数[有效组为(4.5±1.3)×10~9/L,无效组为(4.2±1.0)×10~9/L]比较差异有统计学意义(时间效应的F值分别为30.80和46.08,P均<0.01),血中PAI-1、t-PA和TGF-β_1在注药前后比较无明显差异.胸腔积液中PAI-1在注药后24 h[有效组为(2195±861)μg/L,无效组为(1099±568)μg/L]、注药后72 h[有效组为(1688±703)μg/L,无效组为(1383±797)μg/L]与注药前[有效组为(1054±1039)μg/L,无效组(1027±955)μg/L]比较差异有统计学意义(时间效应的F=6.29,P=0.01);胸腔积液中t-PA在注药后24 h[有效组为(49±49)μg/L,无效组为(53±40)μg/L]、注药后72 h[有效组为(17±20)μg/L,无效组为(28±22)μg/L]与注药前[有效组为(42±33)μg/L,无效组为(54±25)μg/L]比较差异有统计学意义(时间效应的F=19.85,P<0.01);TGF-β1水平给药前后无明显差异;给药后24 h胸腔积液中白细胞计数[有效组为(4.7±4.7)×10~9/L,无效组为(2.1±1.4)×10~9/L]与注药前[有效组为(2.3±1.9)×10~9/L,无效组为(1.0±0.9)×10~9/L]比较差异有统计学意义(F=8.05,P<0.01).平阳霉素胸膜固定术不同疗效组外周血白细胞和中性粒细胞计数及PAI-1、t-PA、TGF-β1的水平在不同时间点无明显差异.胸膜腔内注射平阳霉素后,通过应用重复测最方法计算不同时间点胸腔积液中PAI-1水平,有效组和无效组比较差异有统计学意义(F=8.51,P<0.01),而两组其他指标比较无明显差异.结论 平阳霉素胸膜固定术是一种安全、有效的治疗MPE的方法.胸膜腔内注射平阳霉素后可通过抑制纤溶酶原的活性而达到粘连胸膜的效果.

abstractsObjective To observe the changes of the concentrations of plasminogen activator inhibitor-1(PAI-1), tissue-type plasminogen activator(t-PA), transforming growth factor-β_1 (TGF-β_1) in peripheral blood and pleural effusion before and after intrapleural pingyangmyein administration, and therefore to investigate the mechanism by which pingyangmycin produces pleurodesis. Methods Since February to September 2008, a total of 26 patients with malignant pleura] effusion (MPE) underwent intrapleural pingyangmycin administration. The concentrations of PAI-1, t-PA, TGF-β_1 and the number of leucocytes in peripheral blood and pleura] effusion before and after treatment were detected. The pleurodesis efficacy according to WHO standard was evaluated 1 month later. Patients who showed complete disappearance of pleural effusion lasting more than 1 month and reduction of pleura] effusion more than 50% were classified as the effective group, while the others were classified as the failure group. Results One month after intrapleural pingyangmyein administration, the total response rate of MPE control was 57.7% (effective group = 15 cases). The number of leucocytes and neutrophils in peripheral blood were significantly higher after intrapleural pingyangmycin administration [the number of leucocytes: effective group (9.2±2.0)×10~9/L, failure group (9.4±3.8)×10~9/L; neutrophil count: effective group (7.9± 2.1)×10~9/L, failure group (8.1±3.3)×10~9/L] than in those before [the number of leucocytes: effective group (6.6±1.4)×10~9/L, failure group (5.6±0.9)×10~9/L; neutrophil count: effective group (4.5± 1.3) ×10~9/L, failure group (4.2±1.0)×10~9/L. F = 30.80,46.08 respectively, all P < 0.01]. However, the concentrations of PAId, t-PA and TGF-β_1 in the peripheral blood showed no significant difference before and after treatment(P >0.05). The concentrations of PAI-1 were significantly lower in the pleural effusion before treatment [effective group (1054±1039) μg/L, failure group (1027±955) μg/L] than after treatment [24 h after intrapleura] pingyangmycin administration: effective group (2195±861)μg/L, failure group (1099±568) μg/L] ; 72 h after treatment: effective group (1688±703) μg/L, failure group (1383±797) μg/L (F=6.29, P=0.01). The levels of t-PA were significantly higher in the pleural effusion before treatment[the effective group (42±33) μg/L, failure group (54±25) μg/L] than after treatment [24 h after intrapleural pingyangmycin administration: the effective group (49±49) μg/L, failure group (53±40) μg/L; 72 h after treatment: the effective group (17±20) μg/L, failure group (28±22) μg/L(F=19.85, P <0.01). The levels of TGF-β_1 in the pleural effusion showed no significant difference before and after treatment (P > 0.05). The number of leucocytes in pleural effusion was significantly higher after intrapleura] pingyangmycin administration [the effective group (4.7±4.7)×10~9/L, failure group (2.1±1.4)×10~9/L] than before [the effective group (2.3±1.9)×10~9/L, failure group (1.0±0.9)× 10~9/L. F=8.05, P <0.01]. The number of leucocytes, neutrophils and the concentrations of PAI-1, t-PA, TGF-β_1 in the peripheral blood showed no significant difference between the effective group and the failure group before and after treatment (P > 0.05). However, the concentrations of PAI-1 in pleural effusion after treatment were higher in the effective group than in the failure group (F = 8.51, P < 0.01). Conclusion Intrapleura] pingyangmycin administration is a safe and effective treatment for MPE. The mechanism of pleurodesis is related to inhibiting the activity of plasminogen in the pleural cavity.