Zhu Qing-Qing, Sun Geng-Yun
Department of Respiratory Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2009 Sep;32(9):674-8.
To observe the changes of the concentrations of plasminogen activator inhibitor-1(PAI-1), tissue-type plasminogen activator(t-PA), transforming growth factor-beta(1)(TGF-beta(1)) in peripheral blood and pleural effusion before and after intrapleural pingyangmycin administration, and therefore to investigate the mechanism by which pingyangmycin produces pleurodesis.
Since February to September 2008, a total of 26 patients with malignant pleural effusion (MPE) underwent intrapleural pingyangmycin administration. The concentrations of PAI-1, t-PA, TGF-beta(1) and the number of leucocytes in peripheral blood and pleural 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 pleural effusion more than 50% were classified as the effective group, while the others were classified as the failure group.
One month after intrapleural pingyangmycin 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) x 10(9)/L, failure group (9.4 +/- 3.8) x 10(9)/L; neutrophil count: effective group (7.9 +/- 2.1) x 10(9)/L, failure group (8.1 +/- 3.3) x 10(9)/L] than in those before[the number of leucocytes: effective group (6.6 +/- 1.4) x 10(9)/L, failure group (5.6 +/- 0.9) x 10(9)/L; neutrophil count: effective group (4.5 +/- 1.3) x 10(9)/L, failure group (4.2 +/- 1.0) x 10(9)/L. F = 30.80, 46.08 respectively, all P < 0.01]. However, the concentrations of PAI-1, t-PA and TGF-beta(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) microg/L, failure group (1027 +/- 955) microg/L] than after treatment [24 h after intrapleural pingyangmycin administration: effective group (2195 +/- 861) microg/L, failure group (1099 +/- 568) microg/L]; 72 h after treatment: effective group (1688 +/- 703) microg/L, failure group (1383 +/- 797) microg/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) microg/L, failure group (54 +/- 25) microg/L] than after treatment[24 h after intrapleural pingyangmycin administration: the effective group (49 +/- 49) microg/L, failure group (53 +/- 40) microg/L; 72 h after treatment: the effective group (17 +/- 20) microg/L, failure group (28 +/- 22) microg/L (F = 19.85, P < 0.01). The levels of TGF-beta(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 intrapleural pingyangmycin administration [the effective group (4.7 +/- 4.7) x 10(9)/L, failure group (2.1 +/- 1.4) x 10(9)/L] than before [the effective group (2.3 +/- 1.9) x 10(9)/L, failure group (1.0 +/- 0.9) x 10(9)/L. F = 8.05, P < 0.01]. The number of leucocytes, neutrophils and the concentrations of PAI-1, t-PA, TGF-beta(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).
Intrapleural 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.
观察胸腔内注入平阳霉素前后外周血及胸腔积液中纤溶酶原激活物抑制剂-1（PAI-1）、组织型纤溶酶原激活物（t-PA）、转化生长因子-β1（TGF-β1）浓度的变化，探讨平阳霉素产生胸膜固定术的机制。
2008年2月至9月，共26例恶性胸腔积液（MPE）患者接受胸腔内注入平阳霉素治疗。检测治疗前后外周血及胸腔积液中PAI-1、t-PA、TGF-β1浓度及白细胞计数。1个月后根据WHO标准评估胸膜固定术疗效。胸腔积液完全消失持续超过1个月且胸腔积液减少超过50%的患者分为有效组，其余患者分为无效组。
胸腔内注入平阳霉素1个月后，MPE控制的总有效率为57.7%（有效组15例）。胸腔内注入平阳霉素后外周血白细胞及中性粒细胞计数显著高于治疗前[白细胞计数：有效组（9.2±2.0）×10⁹/L，无效组（9.4±3.8）×10⁹/L；中性粒细胞计数：有效组（7.9±2.1）×10⁹/L，无效组（8.1±3.3）×10⁹/L]，治疗前分别为[白细胞计数：有效组（6.6±1.4）×10⁹/L，无效组（5.6±0.9）×10⁹/L；中性粒细胞计数：有效组（4.5±1.3）×10⁹/L，无效组（4.2±1.0）×10⁹/L。F值分别为30.80、46.08，均P<0.01]。然而，外周血中PAI-1、t-PA和TGF-β1浓度治疗前后差异无统计学意义（P>0.05）。治疗前胸腔积液中PAI-1浓度显著低于治疗后[胸腔内注入平阳霉素后24小时：有效组（2195±861）μg/L，无效组（1099±568）μg/L；治疗后72小时：有效组（1688±703）μg/L，无效组（1383±797）μg/L（F=6.29，P=0.01）]。治疗前胸腔积液中t-PA水平显著高于治疗后[胸腔内注入平阳霉素后24小时：有效组（49±49）μg/L，无效组（53±40）μg/L；治疗后72小时：有效组（17±20）μg/L，无效组（28±22）μg/L（F=19.85，P<0.01）]。胸腔积液中TGF-β1水平治疗前后差异无统计学意义（P>0.05）。胸腔内注入平阳霉素后胸腔积液中白细胞计数显著高于治疗前[有效组（4.7±4.7）×10⁹/L，无效组（2.1±1.4）×10⁹/L]，治疗前分别为[有效组（2.3±1.9）×10⁹/L，无效组（1.0±0.9）×10⁹/L。F=8.05，P<0.01]。治疗前后有效组与无效组外周血白细胞、中性粒细胞及PAI-1、t-PA、TGF-β1浓度差异无统计学意义（P>0.05）。然而，治疗后有效组胸腔积液中PAI-1浓度高于无效组（F=8.51，P<0.01）。
胸腔内注入平阳霉素是治疗MPE的一种安全有效的方法。胸膜固定术的机制与抑制胸腔内纤溶酶原活性有关。
