Effects of dietary cholesterol and simvastatin on cholesterol synthesis in Smith-Lemli-Opitz syndrome.
Effects of dietary cholesterol and simvastatin on cholesterol synthesis in Smith-Lemli-Opitz syndrome.
复制标题
DOI：
10.1203/pdr.0b013e31819ea4eb
复制
发表时间：
2009-06
影响因子：
3.6
通讯作者：
Jones PJ
中科院分区：
文献类型：
--
作者：
Chan YM;Merkens LS;Connor WE;Roullet JB;Penfield JA;Jordan JM;Steiner RD;Jones PJ
胆固醇缺乏和/或 7-脱氢胆固醇 (7-DHC) 过多可能是史密斯-莱姆利-奥皮茨综合征 (SLOS) 病理学的原因。用于改善胆固醇缺乏同时减少 7-DHC 的高胆固醇饮食，以及用于进一步减少甾醇合成的富含胆固醇饮食加辛伐他汀，均已被用作潜在的治疗方法。然而，膳食胆固醇和辛伐他汀对 SLOS 中胆固醇合成的影响尚未见报道。 12 名 SLOS 受试者参与了这项研究：其中 9 名受试者接受高胆固醇饮食 (HI) 3 年，另外 3 名受试者在接受低胆固醇饮食 (LO) 4 周后接受研究。口服氧化氘后，使用气相色谱-同位素比质谱法测量胆固醇分数合成率（FSR）。与LO相比，HI组的FSR较低（HI：1.46±0.62%/d；LO：4.77±0.95%/d；P<0.001）。三名 HI 受试者在服用辛伐他汀 (HI+ST) 0.8 年后重新进行测试。与单独补充胆固醇相比，辛伐他汀倾向于降低FSR并显着降低（P<0.01）血浆7-DHC。该研究证明了氘掺入方法在了解 SLOS 治疗干预效果方面的实用性。数据表明，膳食胆固醇补充剂可减少 SLOS 中的胆固醇合成，并进一步支持用富含胆固醇的饮食和辛伐他汀联合治疗 SLOS 的基本原理。
Deficient cholesterol and/or excessive 7-dehydrocholesterol (7-DHC) may be responsible for the pathology of Smith-Lemli-Opitz syndrome (SLOS). Both high cholesterol diets given to ameliorate cholesterol deficiency while decreasing 7-DHC, and cholesterol-enriched diets plus simvastatin to further decrease sterol synthesis, have been used as potential therapies. However, the effect of dietary cholesterol and simvastatin on cholesterol synthesis in SLOS has not been reported. Twelve SLOS subjects enrolled in the study: Nine had received a high cholesterol diet (HI) for 3 years, and three were studied after 4 weeks on a low cholesterol diet (LO). Cholesterol fractional synthesis rate (FSR) was measured after oral administration of deuterium oxide, using gas-chromatography-isotope ratio mass spectrometry. FSR was lower in HI compared with LO (HI: 1.46±0.62%/d; LO: 4.77±0.95%/d; P<0.001). Three HI subjects were re-tested after 0.8 years taking simvastatin (HI+ST). Simvastatin tended to reduce FSR and significantly decreased (P<0.01) plasma 7-DHC compared to cholesterol supplementation alone. The study demonstrates the utility of the deuterium incorporation method to understand the effect of therapeutic interventions in SLOS. The data suggest that dietary cholesterol supplementation reduces cholesterol synthesis in SLOS and further support the rationale for the combined treatment of SLOS with a cholesterol-enriched diet and simvastatin.