Gary Lee Y C, Teixeira L R, Devin C J, Vaz M A, Vargas F S, Thompson P J, Lane K B, Light R W
Department of Pulmonary Medicine, St. Thomas Hospital and Vanderbilt University, Nashville, Tennessee 37202,
Am J Respir Crit Care Med. 2001 Mar;163(3 Pt 1):640-4. doi: 10.1164/ajrccm.163.3.2002091.
Transforming growth factor-beta2 (TGF-beta2) has recently been shown to produce effective pleurodesis in rabbits. Conventional pleurodesing agents such as talc act by inducing pleural injury, which results in acute inflammation and fibrosis. TGF-beta2 is a profibrotic cytokine capable of producing fibrosis without inducing significant pleural inflammation. We hypothesize that intrapleural administration of TGF-beta2 would (1) produce an effective pleurodesis faster; (2) stimulate more collagen deposition, and (3) induce less inflammation when compared with intrapleural injection of talc. Thirty rabbits were divided into two groups and given either TGF-beta(2) (1.7 microg) or talc slurry (400 mg/kg) via a chest tube. Five rabbits from each group were killed at Days 1, 4, and 7. Gross pleurodesis was graded from 1 (none) to 8 (complete symphysis). The microscopic pleural inflammation and fibrosis were graded from 0 to 4. Pleural thickening and the total area of collagen deposition were compared. Intrapleural injection of TGF-beta2 produced effective pleurodesis within 7 d (median pleurodesis score = 7 at Day 7). At Day 7, TGF-beta2 induced significantly more collagen deposition (19.4 +/- 19.6% versus 4.6 +/- 2.9% of total area of pleura at Day 7), higher pleural fibrosis score (3.0 +/- 1.0 versus 1.8 +/- 0.5), and pleural thickness (286 +/- 191 versus 85 +/- 37 microm) than did talc. There was no difference in the degree of pleural inflammation between the two groups at Day 7 (2.6 +/- 0.9 for TGF-beta2 versus 2.4 +/- 0.6 for talc) or at any other time points. In conclusion, the intrapleural administration of TGF-beta2 produced excellent pleurodesis in rabbits at a rate faster than talc slurry and all other pleurodesing agents investigated before. TGF-beta2 stimulated more collagen deposition without inducing excess inflammation when compared with talc slurry. TGF-beta2 may have advantages over talc slurry in the management of recurrent pleural effusion and pneumothorax.
转化生长因子-β2(TGF-β2)最近已被证明可在兔体内产生有效的胸膜固定术。传统的胸膜固定剂如滑石粉通过诱导胸膜损伤起作用,这会导致急性炎症和纤维化。TGF-β2是一种促纤维化细胞因子,能够在不引起明显胸膜炎症的情况下产生纤维化。我们假设,与经胸腔注射滑石粉相比,经胸腔给予TGF-β2将(1)更快地产生有效的胸膜固定术;(2)刺激更多的胶原蛋白沉积,以及(3)引起更少的炎症。将30只兔分为两组,通过胸管分别给予TGF-β2(1.7微克)或滑石粉悬液(400毫克/千克)。每组5只兔分别在第1、4和7天处死。大体胸膜固定术从1级(无)到8级(完全融合)进行分级。微观胸膜炎症和纤维化从0到4级进行分级。比较胸膜增厚和胶原蛋白沉积的总面积。经胸腔注射TGF-β2在7天内产生了有效的胸膜固定术(第7天胸膜固定术评分中位数 = 7)。在第7天,与滑石粉相比,TGF-β2诱导了显著更多的胶原蛋白沉积(第7天占胸膜总面积的19.4±19.6% 对4.6±2.9%)、更高的胸膜纤维化评分(3.0±1.0对1.8±0.5)和胸膜厚度(286±191对85±37微米)。两组在第7天(TGF-β2为2.6±0.9,滑石粉为2.4±0.6)或任何其他时间点的胸膜炎症程度均无差异。总之,经胸腔给予TGF-β2在兔体内产生了优异的胸膜固定术,其速度比滑石粉悬液和之前研究的所有其他胸膜固定剂都快。与滑石粉悬液相比,TGF-β2刺激了更多的胶原蛋白沉积,而不会引起过度炎症。在复发性胸腔积液和气胸的治疗中,TGF-β2可能比滑石粉悬液具有优势。