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洛伐他汀不能纠正肾上腺脑白质营养不良蛋白缺陷小鼠组织中极长链脂肪酸的蓄积。

Lovastatin does not correct the accumulation of very long-chain fatty acids in tissues of adrenoleukodystrophy protein-deficient mice.

作者信息

Yamada T, Shinnoh N, Taniwaki T, Ohyagi Y, Asahara H, Kira J

机构信息

Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

J Inherit Metab Dis. 2000 Sep;23(6):607-14. doi: 10.1023/a:1005634130286.

Abstract

Lovastatin, an inhibitor of 3-hydroxy-3-methylglutarylcoenzyme A reductase, normalizes the very long-chain fatty acids (VLCFA) concentrations in fibroblasts and plasma from patients with X-linked adrenoleukodystrophy (X-ALD). The effects of lovastatin on the accumulation of VLCFA in tissues of adrenoleukodystrophy protein (ALDP)-deficient mice were assessed. ALDP-deficient mice were fed chow with 0.01-0.1% lovastatin for 4-8 weeks. The VLCFA concentrations in the plasma, brain, spinal cord, liver and kidneys were measured. Treatment with 0.1% lovastatin significantly reduced body weight and total cholesterol in the plasma of ALDP-deficient mice. Treatment with lovastatin, however, did not correct the accumulation of VLCFA in the plasma or tissues, including the brain and spinal cord. Lovastatin does not affect the accumulation of VLCFA in ALDP-deficient tissues in mice.

摘要

洛伐他汀是3-羟基-3-甲基戊二酰辅酶A还原酶的抑制剂,可使X连锁肾上腺脑白质营养不良(X-ALD)患者成纤维细胞和血浆中的极长链脂肪酸(VLCFA)浓度正常化。评估了洛伐他汀对肾上腺脑白质营养不良蛋白(ALDP)缺陷小鼠组织中VLCFA积累的影响。给ALDP缺陷小鼠喂食含0.01-0.1%洛伐他汀的食物4-8周。测量血浆、脑、脊髓、肝脏和肾脏中的VLCFA浓度。用0.1%洛伐他汀治疗可显著降低ALDP缺陷小鼠血浆中的体重和总胆固醇。然而,用洛伐他汀治疗并未纠正血浆或包括脑和脊髓在内的组织中VLCFA的积累。洛伐他汀不影响ALDP缺陷小鼠组织中VLCFA的积累。

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