Vanhanen H, Kesäniemi Y A, Miettinen T A
Second Department of Medicine, University of Helsinki, Finland.
Metabolism. 1992 Jun;41(6):588-95. doi: 10.1016/0026-0495(92)90050-k.
Serum lipids, and absorption, intestinal fluxes, fecal elimination, and synthesis of cholesterol were studied before and during 4 weeks of pravastatin treatment at a dose of 40 mg/d in heterozygous familial hypercholesterolemic (FH) patients without (control group, n = 7) and with an ileal bypass (IBP group, n = 6). The drug reduced serum total and low-density lipoprotein (LDL) cholesterol and LDL-apoprotein (apo)B levels up to 34%. Less-consistent decreases in intermediate-density lipoprotein (IDL) and very-low-density lipoprotein (VLDL) cholesterol were also seen. None of the control patients and two of the IBP patients became normolipidemic (LDL less than 4 mmol/L). Marked transient reductions in serum free-methylated-cholesterol precursors, and more-constant decreases in the esterified and total fractions, suggested that cholesterol synthesis was reduced shortly after the start of treatment. The decreases in total lathosterol and methylsterols were more extensive in the IBP group than in the control group. Serum plant sterol levels were slightly increased, with inconsistent elevations of cholestanol. Reduced fecal elimination of cholesterol and its precursors suggests that decreased cholesterol synthesis was mainly due to lowered bile acid production, particularly in the IBP group with markedly enhanced basal bile acid and cholesterol synthesis. The serum and fecal levels of cholesterol precursors, lathosterol in particular, were related to each other and were proportionate to the serum level and fecal elimination of cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)
在40毫克/天剂量的普伐他汀治疗前及治疗4周期间，对杂合子家族性高胆固醇血症（FH）患者进行了研究，这些患者分为两组，一组无回肠旁路手术（对照组，n = 7），另一组有回肠旁路手术（IBP组，n = 6），研究内容包括血清脂质以及胆固醇的吸收、肠道通量、粪便排泄和合成情况。该药物使血清总胆固醇和低密度脂蛋白（LDL）胆固醇以及LDL-载脂蛋白（apo）B水平降低达34%。中间密度脂蛋白（IDL）和极低密度脂蛋白（VLDL）胆固醇也有不太一致的降低。对照组患者无一例血脂正常（LDL低于4毫摩尔/升），IBP组有两例血脂正常。血清游离甲基化胆固醇前体明显短暂降低，酯化和总部分则持续降低，这表明治疗开始后不久胆固醇合成减少。IBP组总羊毛甾醇和甲基甾醇的降低比对照组更显著。血清植物甾醇水平略有升高，胆甾烷醇升高情况不一致。胆固醇及其前体的粪便排泄减少表明胆固醇合成减少主要是由于胆汁酸生成降低，特别是在基础胆汁酸和胆固醇合成明显增强的IBP组。胆固醇前体的血清和粪便水平，尤其是羊毛甾醇，相互关联，且与血清胆固醇水平和粪便胆固醇排泄成比例。（摘要截短于250字）
