Bauer E P, Kuki S, Arras M, Zimmerman R, Schaper W
Division of Cardiothoracic Surgery, Max-Planck-Institute for Clinical and Physiological Research, Kerckhoff-Clinic, Bad Nauheim, Germany.
Eur J Cardiothorac Surg. 1997 May;11(5):818-23. doi: 10.1016/s1010-7940(97)01180-9.
Several mechanisms are known to produce mechanical stress during and after cardiac surgery, e.g. aortic cross-clamping and pulmonary artery banding (PAB). However, little is known about the transcription of myocardial genes which are changed during mechanical overload. This study was performed to investigate growth factor mRNA expression after PAB in porcine hearts.
The experiment was performed in 35 pigs (five groups). Each group consisted of three sham-pigs (S-pigs) and four banding-pigs (B-pigs). The mean transbanding gradient in B-pigs was 29 +/- 2.5 mm Hg. The hearts were excised after different time intervals. The probes were snap-frozen in liquid nitrogen and stored at -80 degrees C. Analysis was performed by Northern blot.
Right ventricular weight increased significantly after 7 and 24 days (P < 0.05). There was an upregulation of transcriptional and growth factors in B-pigs: c-jun mRNA: 412 +/- 12.1% after 2 h (P < 0.001); c-fos mRNA: 303 +/- 18.5% after 2 h (P < 0.001); vascular endothelial growth factor (VEGF) mRNA: 203 +/- 18.2% after 2 h (P < 0.001); Flk-1 mRNA: 156 +/- 16% after 2 h (P < 0.05), 253 +/- 5% after 24 h (P < 0.01) and 184 +/- 12% after 3 days (P < 0.01); transforming growth factor-beta1 (TGF-beta1) mRNA: 255 +/- 21.5% after 24 h (P < 0.002). Fibroblast growth factors 1 and 2 (FGF-1 and FGF-2) were constitutively expressed in B- and S-pigs and did not change their expression.
Pulmonary artery banding results in significant right ventricular hypertrophy and upregulation of different growth factors. However, growth factors known to induce hypertrophy in vitro, like the FGFs, showed unchanged expression. We think that myocardial growth factors may have trophic functions in the heart which may be useful for cardiac surgery in future.
已知有几种机制可在心脏手术期间及术后产生机械应力,例如主动脉交叉钳夹和肺动脉环扎术(PAB)。然而,对于在机械负荷期间发生变化的心肌基因转录情况知之甚少。本研究旨在调查猪心脏PAB术后生长因子mRNA的表达。
实验在35头猪(分为五组)中进行。每组包括三头假手术猪(S组猪)和四头环扎猪(B组猪)。B组猪的平均环扎后压力阶差为29±2.5 mmHg。在不同时间间隔后取出心脏。将组织样本在液氮中速冻并储存在-80℃。通过Northern印迹法进行分析。
7天和24天后右心室重量显著增加(P<0.05)。B组猪中存在转录因子和生长因子的上调:c-jun mRNA:2小时后为412±12.1%(P<0.001);c-fos mRNA:2小时后为303±18.5%(P<0.001);血管内皮生长因子(VEGF)mRNA:2小时后为203±18.2%(P<0.001);Flk-1 mRNA:2小时后为156±16%(P<0.05),24小时后为253±5%(P<0.01),3天后为184±12%(P<0.01);转化生长因子-β1(TGF-β1)mRNA:24小时后为255±21.5%(P<0.002)。成纤维细胞生长因子1和2(FGF-1和FGF-2)在B组猪和S组猪中均持续表达,且其表达未发生变化。
肺动脉环扎导致显著的右心室肥厚和不同生长因子的上调。然而,已知在体外可诱导肥厚的生长因子,如FGFs,其表达未发生变化。我们认为心肌生长因子可能在心脏中具有营养功能,这可能对未来的心脏手术有用。