Lee Y C Gary, Yasay Justin R, Johnson Joyce E, Parker Richard E, Thompson Philip J, Lane Kirk B, Light Richard W
Department of Pulmonary Medicine, St Thomas Hospital, Nashville, Tennessee, USA.
Respirology. 2002 Sep;7(3):209-16. doi: 10.1046/j.1440-1843.2002.00397.x.
Transforming growth factor (TGF)-beta2 can produce effective pleurodesis in animals, but its efficacy has not been compared with commonly used pleurodesing agents in sheep, which have a thick pleura resembling that of humans. The acute physiological effects and the level of systemic TGF-beta absorption after its intrapleural administration have not been studied. The aims of the present study were to compare: (i) the effectiveness of TGF-beta2, talc and bleomycin in producing pleurodesis in sheep; (ii) the acute side-effects and systemic TGF-beta levels following the intrapleural administration of these agents; and (iii) histological changes after intrapleural injections of these agents.
Twelve sheep were divided into three groups and were given a single intrapleural dose of TGF-beta2 (0.25 microg/kg), talc slurry (5 g) or bleomycin (60 IU) via a chest tube. Saline or buffer was injected into the contralateral side, which served as the control. Arterial blood gases and respiratory and heart rates were monitored for the first 24 h. Plasma levels of TGF-beta1 and TGF-beta2 were measured. Pleurodesis was graded macroscopically from 1 (none) to 8 (symphysis > 50% of hemithorax) at day 14.
At day 14, the pleurodesis score of the TGF-beta2 group (7.7+/-0.6) was similar to that of the talc (7.0+/-1.7) group and significantly higher than that of the bleomycin group (3.3+/-2.3; P < 0.05). No significant differences were seen in arterial blood gas analysis, vital signs and plasma TGF-beta1 and TGF-beta2 concentrations among the three groups.
Transforming growth factor-beta2 was as effective as talc and more so than bleomycin in inducing pleurodesis in sheep. Intrapleural administration of TGF-beta2 appeared safe. No acute changes in gaseous exchange or macroscopic abnormalities were seen following intrapleural TGF-beta2. Importantly, there was no evidence of an increase in systemic TGF-beta levels following its intrapleural administration.
转化生长因子(TGF)-β2可在动物体内产生有效的胸膜固定术,但其疗效尚未与绵羊中常用的胸膜固定剂进行比较,绵羊的胸膜较厚,类似于人类。其胸膜腔内给药后的急性生理效应和全身TGF-β吸收水平尚未得到研究。本研究的目的是比较:(i)TGF-β2、滑石粉和博来霉素在绵羊中产生胸膜固定术的有效性;(ii)这些药物胸膜腔内给药后的急性副作用和全身TGF-β水平;(iii)这些药物胸膜腔内注射后的组织学变化。
将12只绵羊分为三组,通过胸管给予单次胸膜腔内剂量的TGF-β2(0.25微克/千克)、滑石粉浆(5克)或博来霉素(60国际单位)。向对侧注入生理盐水或缓冲液作为对照。在最初24小时监测动脉血气、呼吸和心率。测量血浆中TGF-β1和TGF-β2的水平。在第14天,从宏观上对胸膜固定术进行分级,从1(无)到8(粘连>半侧胸腔的50%)。
在第14天,TGF-β2组的胸膜固定术评分(7.7±0.6)与滑石粉组(7.0±1.7)相似,且显著高于博来霉素组(3.3±2.3;P<0.05)。三组之间在动脉血气分析、生命体征以及血浆TGF-β1和TGF-β2浓度方面未见显著差异。
转化生长因子-β2在诱导绵羊胸膜固定术方面与滑石粉效果相当,且比博来霉素更有效。胸膜腔内给予TGF-β2似乎是安全的。胸膜腔内给予TGF-β2后未观察到气体交换的急性变化或宏观异常。重要的是,没有证据表明胸膜腔内给予TGF-β2后全身TGF-β水平会升高。