März W, Siekmeier R, Müller H M, Wieland H, Gross W, Olbrich H G
Division of Clinical Chemistry, Department of Medicine, Albert Ludwigs-University, Freiburg, Germany.
J Cardiovasc Pharmacol Ther. 2000 Oct;5(4):275-9. doi: 10.1054/JCPT.2000.16695.
Cardiomyopathic hamsters develop heart disease early in life, which leads to congestive heart failure and death as these hamsters age. Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been reported to reduce ubiquinone concentrations and to deteriorate myocardial function in humans and in experimental animals. HMG-CoA reductase inhibitors differ regarding their ability to penetrate extrahepatic tissues. As a consequence, lovastatin inhibits cholesterol biosynthesis at least 100-fold more effectively than pravastatin in extrahepatic cells. We examined the effect of lovastatin and pravastatin (approximately 10 mg per kilogram of body weight and per day mixed in the diet) compared with controls on the lifespan of cardiomyopathic hamsters (BIO 8262 strain) in the heart-failure period. In male hamsters, neither lovastatin nor pravastatin significantly affected survival. In female hamsters, lovastatin reduced median survival time from 89 days (control animals) to 30 days (P <.05); pravastatin (median survival, 115 days) had no statistically significant effect. We conclude that lovastatin, but not pravastatin, at a daily dose of 10 mg per kilogram of body weight significantly increases the mortality of cardiomyopathic hamsters. This effect may be the result of inhibition of myocardial ubiquinone supply.
患心肌病的仓鼠在生命早期就会患上心脏病，随着年龄增长，会导致充血性心力衰竭和死亡。据报道，羟甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂会降低人体内和实验动物体内的泛醌浓度，并使心肌功能恶化。HMG-CoA还原酶抑制剂穿透肝外组织的能力有所不同。因此，洛伐他汀在肝外细胞中抑制胆固醇生物合成的效率至少比普伐他汀高100倍。我们研究了在心力衰竭期，与对照组相比，洛伐他汀和普伐他汀（每天每千克体重约10毫克，混入饲料中）对患心肌病的仓鼠（BIO 8262品系）寿命的影响。在雄性仓鼠中，洛伐他汀和普伐他汀均未显著影响其存活率。在雌性仓鼠中，洛伐他汀将中位生存时间从89天（对照动物）缩短至30天（P <.05）；普伐他汀（中位生存时间为115天）没有统计学上的显著影响。我们得出结论，每天每千克体重10毫克的洛伐他汀会显著增加患心肌病仓鼠的死亡率，而普伐他汀则不会。这种影响可能是抑制心肌泛醌供应的结果。
