Lopes Jackson B, Dallan Luis A O, Campana-Filho Sérgio P, Lisboa Luiz A F, Gutierrez Paulo S, Moreira Luiz Felipe P, Oliveira Sergio A, Stolf Noedir A G
Division of Cardiothoracic Surgery, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.
Eur J Cardiothorac Surg. 2009 Feb;35(2):313-8. doi: 10.1016/j.ejcts.2008.09.046. Epub 2008 Nov 12.
Several methods have been utilized to prevent pericardial and retrosternal adhesions, but none of them evaluated the mesothelial regenerative hypothesis. There are evidences that the mesothelial trauma reduces pericardial fibrinolytic capability and induces an adhesion process. Keratinocyte growth factor (KGF) has proven to improve mesothelial cells proliferation. This study investigated the influence of keratinocyte growth factor in reducing post-surgical adhesions.
Twelve pigs were operated and an adhesion protocol was employed. Following a stratified randomization, the animals received a topical application of KGF or saline. At 8 weeks, intrapericardial adhesions were evaluated and a severity score was established. The time spent to dissect the adhesions and the amount of sharp dissection used, were recorded. Histological sections were stained with sirius red and morphometric analyses were assessed with a computer-assisted image analysis system.
The severity score was lower in the KGF group than in the control group (11.5 vs 17, p=0.005). The dissection time was lower in the KGF group (9.2+/-1.4 min vs 33.9+/-9.2 min, p=0.004) and presented a significant correlation with the severity score (r=0.83, p=0.001). A significantly less sharp dissection was also required in the KGF group. Also, adhesion area and adhesion collagen were significantly lower in the KGF group than in the control group.
The stimulation of pericardial cells with KGF reduced the intensity of postoperative adhesions and facilitated the re-operation. This study suggests that the mesothelial regeneration is the new horizon in anti-adhesion therapies.
已经采用了几种方法来预防心包和胸骨后粘连，但没有一种方法评估间皮再生假说。有证据表明，间皮损伤会降低心包纤维蛋白溶解能力并引发粘连过程。角质形成细胞生长因子（KGF）已被证明可促进间皮细胞增殖。本研究调查了角质形成细胞生长因子在减少术后粘连方面的影响。
对12头猪进行手术并采用粘连方案。经过分层随机分组后，动物接受KGF或生理盐水的局部应用。在8周时，评估心包内粘连情况并建立严重程度评分。记录分离粘连所需的时间和使用的锐性分离量。组织学切片用天狼星红染色，并用计算机辅助图像分析系统进行形态计量分析。
KGF组的严重程度评分低于对照组（11.5对17，p = 0.005）。KGF组的分离时间较短（9.2±1.4分钟对33.9±9.2分钟，p = 0.004），并且与严重程度评分呈显著相关性（r = 0.83，p = 0.001）。KGF组所需的锐性分离也明显较少。此外，KGF组的粘连面积和粘连胶原蛋白明显低于对照组。
用KGF刺激心包细胞可降低术后粘连的强度并便于再次手术。本研究表明，间皮再生是抗粘连治疗的新方向。
