Increased oxysterol contents in diabetic rat hearts: their involvement in diabetic cardiomyopathy.
Increased oxysterol contents in diabetic rat hearts: their involvement in diabetic cardiomyopathy.
复制标题
糖尿病大鼠心脏中氧甾醇含量增加：它们与糖尿病心肌病有关。
DOI：
--
复制
发表时间：
1997
影响因子：
6.2
通讯作者：
Takayuki Ito
中科院分区：
文献类型：
--
作者：
Hiroyuki Matsui;Kenji Okumura;H. Mukawa;M. Hibino;Y. Toki;Takayuki Ito
背景
与糖尿病相关的脂质代谢异常被认为参与了糖尿病心肌病的发病机制。氧固醇是胆固醇的氧化衍生物，已知具有高度细胞毒性。
目的
监测糖尿病大鼠心肌氧固醇的变化，并评价降脂药普罗布考对糖尿病大鼠心肌脂质和氧固醇的影响。
方法和结果
将链脲佐菌素诱导的糖尿病大鼠分为两组;一组给予标准饮食，另一组给予含1%（重量/重量）普罗布考的饮食8周。通过毛细管气相色谱法在心肌中鉴定出两种氧固醇，7 β-羟基胆固醇和7-酮胆固醇。糖尿病大鼠的7 β-羟基胆固醇和7-酮胆固醇均显著增加（分别为49.9 +/- 9.4 ng/mg干重vs 5.8 +/- 1.2 ng/mg干重，P < 0.05; 5.3 +/- 1.2 ng/mg干重vs 1.7 +/- 0.1 ng/mg干重，P < 0.01）。普罗布考不仅降低血脂，而且心肌脂质，胆固醇和鞘磷脂组分除外。但普罗布考不能改善胰岛素缺乏、糖代谢和心肌氧固醇含量。
结论
这项研究表明糖尿病大鼠心肌中氧化固醇的增加，表明氧化固醇可能在糖尿病心肌病的发展中发挥作用。在本研究中使用的剂量下，普罗布考没有降低心肌氧固醇含量，这表明氧固醇的增加可能不是由于脂质的高循环浓度，而是由于胰岛素缺乏引起的心肌代谢紊乱。
BACKGROUND
Abnormal lipid metabolism associated with diabetes mellitus has been proposed to be involved in the pathogenesis of diabetic cardiomyopathy. Oxysterols, oxidation derivatives of cholesterol, are known to be highly cytotoxic.
OBJECTIVE
To monitor changes in myocardial oxysterols and to assess the effect of probucol, a lipid lowering agent, on myocardial lipids and oxysterols in diabetic rats.
METHODS AND RESULTS
Streptozotocin-induced diabetic rats were divided into two groups; one group was put on a standard diet, and the other a diet containing 1% (weight/weight) probucol for eight weeks. Two oxysterols, 7 beta-hydroxycholesterol and 7-ketocholesterol, were identified in myocardium by capillary gas chromatography. Both 7 beta-hydroxycholesterol and 7-ketocholesterol were significantly increased in diabetic rats (49.9 +/- 9.4 ng/mg dry weight versus 5.8 +/- 1.2 in controls, P < 0.05; and 5.3 +/- 1.2 ng/mg dry weight versus 1.7 +/- 0.1 in controls, P < 0.01, respectively). Probucol reduced not only plasma lipids but also myocardial lipids except for cholesterol and sphingomyelin fractions. However, probucol did not improve insulin deficiency, glucose metabolism or myocardial oxysterol contents.
CONCLUSIONS
This study demonstrated an increase in oxysterols in the myocardium of diabetic rats, suggesting that oxysterols may play a role in the development of diabetic cardiomyopathy. Probucol did not decrease the myocardial oxysterol content at the dose used in this study, suggesting that the increase in oxysterols may not be attributed to high circulating concentrations of lipids, but rather to disturbed myocardial metabolism due to insulin deficiency.