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猪肺动脉环扎术后心肌基因转录的上调与下调

Upregulated and downregulated transcription of myocardial genes after pulmonary artery banding in pigs.

作者信息

Bauer E P, Kuki S, Zimmermann R, Schaper W

机构信息

Division of Thoracic and Cardiovascular Surgery, Max-Planck-Institute, Kerckhoff-Clinic, Bad Nauheim, Germany.

出版信息

Ann Thorac Surg. 1998 Aug;66(2):527-31. doi: 10.1016/s0003-4975(98)00445-7.

Abstract

BACKGROUND

Acute or chronic pressure overload may occur during or after cardiac surgical procedures. Typical examples are aortic cross-clamping and pulmonary artery banding. It is well known that mechanical stress induces transcription of different myocardial genes. However, these results were mainly obtained from in vitro studies and experiments with rodents. This experiment was carried out to investigate molecular alterations after pressure overload in porcine hearts.

METHODS

The study was performed with 35 Landrace pigs with a mean weight of 32+/-1.2 kg. The five groups consisted of 7 pigs each, 3 sham-operated pigs and 4 banded pigs. The hearts were exised after different time intervals. We investigated messenger RNA expression of sarcoplasmic reticulum adenosine triphosphatase, phospholamban, alpha-/beta-myosin heavy chain, and atrial natriuretic factor by Northern blot analysis.

RESULTS

The ratio of right ventricular weight to body weight increased significantly after 7 and 24 days in banded pigs (p < 0.05). Atrial natriuretic factor messenger RNA was significantly upregulated in banded pigs versus sham-operated pigs after 1 day (240%+/-7% versus 100%+/-6%; p < 0.01) and 3 days (520%+/-8% versus 100%+/-8%; p < 0.01). There was insignificant downregulation of sarcoplasmic reticulum adenosine triphosphatase and phospholamban after 1, 3, and 7 days. Myosin heavy chain messenger RNA expression remained unchanged.

CONCLUSIONS

Pulmonary artery banding results in hypertrophic response of the porcine right ventricle; however, the weight increase is not the result of myosin heavy chain messenger RNA upregulation. Atrial natriuretic factor messenger RNA is locally expressed in mechanically stressed myocytes. Furthermore, pressure overload downregulates transcription of calcium-binding proteins that can influence ventricular contractility. These results may have an impact on cardiac surgical procedures.

摘要

背景

急性或慢性压力超负荷可能在心脏外科手术期间或之后发生。典型例子是主动脉交叉钳夹和肺动脉束带术。众所周知,机械应力可诱导不同心肌基因的转录。然而,这些结果主要来自体外研究和啮齿动物实验。本实验旨在研究猪心脏压力超负荷后的分子变化。

方法

该研究使用了35头平均体重为32±1.2千克的长白猪。五组每组7头猪,其中3头为假手术猪,4头为束带猪。在不同时间间隔后取出心脏。我们通过Northern印迹分析研究了肌浆网三磷酸腺苷酶、受磷蛋白、α/β-肌球蛋白重链和心钠素的信使核糖核酸表达。

结果

束带猪在7天和24天后右心室重量与体重之比显著增加(p<0.05)。与假手术猪相比,束带猪在心钠素信使核糖核酸在1天(240%±7%对100%±6%;p<0.01)和3天(520%±8%对100%±8%;p<0.01)后显著上调。在1、3和7天后,肌浆网三磷酸腺苷酶和受磷蛋白有不显著的下调。肌球蛋白重链信使核糖核酸表达保持不变。

结论

肺动脉束带导致猪右心室肥厚反应;然而,重量增加不是肌球蛋白重链信使核糖核酸上调的结果。心钠素信使核糖核酸在机械应激的心肌细胞中局部表达。此外,压力超负荷下调可影响心室收缩力的钙结合蛋白的转录。这些结果可能对心脏外科手术有影响。

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