实验性诱导的心脏肥大和衰竭大鼠的骨骼肌异常

Skeletal muscle abnormalities in rats with experimentally induced heart hypertrophy and failure.

作者信息

Bernocchi Palmira, Cargnoni Anna, Vescovo Giorgio, Dalla Libera Luciano, Parrinello Giovanni, Boraso Antonella, Ceconi Claudio, Ferrari Roberto

机构信息

Cardiovascular Research Centre, Fondazione S. Maugeri, IRCCS, 25064 Gussago (Brescia), Italy.

出版信息

Basic Res Cardiol. 2003 Mar;98(2):114-23. doi: 10.1007/s003950300001.

DOI:10.1007/s003950300001

PMID:12607133

Abstract

BACKGROUND

In congestive heart failure (CHF), function and metabolism of skeletal muscles are abnormal.

AIM

To evaluate whether the reduced oxidative capacity of skeletal muscles in CHF is due to impaired O(2) utilisation.

METHODS

CHF was induced in rats by injecting 50 mg/Kg monocrotaline. Several animals received the same dose of monocrotaline but only compensated right ventricular hypertrophy and no sign of congestion resulted. Two age- and diet-matched groups of control animals were also studied. In soleus and extensor digitorum longus (EDL) muscles, we studied skeletal muscle blood flow, oxidative capacity and respiratory function of skinned muscle fibres.

RESULTS

In CHF, we observed a decrease of muscle blood flow (statistically significant in the soleus, p < 0.05 vs. controls). In compensated rats, a similar trend in blood flow was observed. In both soleus and EDL, a significant reduction of high energy phosphate and a shift of the redox potential towards accumulation of reducing equivalents were observed. The reduction of energy charge was not correlated to the decrease of blood flow. In skinned myofibres, the ratio of O(2) utilised in the presence and in absence of ADP (an index of phoshorilating efficiency) was reduced from 8.9 +/- 1.9 to 2.7 +/- 0.2 (p < 0.001) and from 5.7 +/- 1.0 to 2.0 +/- 0.3 (p < 0.01) in soleus and EDL, respectively. Activity of the different complexes of respiratory chain was investigated by means of specific inhibitors, showing major abnormalities at the level of complex I. In fact, inhibition of VO(2) by rotenone was decreased from 83.5 +/- 3.2 to 36.4 +/- 9.6 % (p < 0.005) and from 81.8 +/- 6.1 to 38.2 +/- 7.4 % (p < 0.005) in soleus and EDL, respectively.

CONCLUSIONS

In rats with CHF, abnormalities of oxidative phosphorylation of muscles occur and complex I of the respiratory chain seem to be primarily affected. The metabolic alterations of skeletal muscles in CHF may be explained, at least in part, by an impaired O(2) utilisation.

摘要

背景

在充血性心力衰竭（CHF）中，骨骼肌的功能和代谢异常。

目的

评估CHF中骨骼肌氧化能力降低是否由于氧利用受损。

方法

通过注射50mg/Kg野百合碱诱导大鼠发生CHF。几只动物接受相同剂量的野百合碱，但仅出现代偿性右心室肥厚且无充血迹象。还研究了两组年龄和饮食匹配的对照动物。在比目鱼肌和趾长伸肌（EDL）中，我们研究了骨骼肌血流、氧化能力和去皮肤肌纤维的呼吸功能。

结果

在CHF中，我们观察到肌肉血流减少（比目鱼肌中具有统计学意义，与对照组相比p<0.05）。在代偿性大鼠中，观察到类似的血流趋势。在比目鱼肌和EDL中，均观察到高能磷酸盐显著减少以及氧化还原电位向还原当量积累的方向转变。能量电荷的降低与血流减少无关。在去皮肤肌纤维中，比目鱼肌和EDL中存在和不存在ADP时的氧利用比率（磷酸化效率指标）分别从8.9±1.9降至2.7±0.2（p<0.001）和从5.7±1.0降至2.0±0.3（p<0.01）。通过特异性抑制剂研究呼吸链不同复合物的活性，显示在复合物I水平存在主要异常。事实上，鱼藤酮对VO₂的抑制在比目鱼肌和EDL中分别从83.5±3.2%降至36.4±9.6%（p<0.005）和从81.8±6.1%降至38.2±7.4%（p<0.005）。