Miettinen T A, Gylling H
University of Helsinki, Helsinki, Finland.
Eur J Clin Invest. 2003 Nov;33(11):976-82. doi: 10.1046/j.1365-2362.2003.01229.x.
Serum contains noncholesterol sterols, which are reliable markers of cholesterol metabolism, but their presence and importance in different lipoproteins have been insufficiently studied.
Serum and lipoprotein cholesterol precursors squalene, cholestanol, desmosterol and lathosterol (markers of cholesterol synthesis) and cholestanol and plant sterols (markers of cholesterol absorption), and absorption efficacy and absolute synthesis of cholesterol were studied at baseline and during 6-month atorvastatin (80 mg day(-1)) treatment by the sterol balance technique in men with type 2 diabetes.
At baseline, approximately 14% of serum squalene was transported by VLDL, 12% by IDL, 40% by LDL and 30% by HDL. The respective values for the noncholesterol sterols were approximately 8, 4, 61 and 26%. The squalene to cholesterol ratios were highest in VLDL and IDL, those of cholestanol, desmosterol and absorption marker sterols were gradually higher, and that of lathosterol lower from VLDL to HDL. Atorvastatin reduced LDL cholesterol by approximately 50%, decreased the absolute cholesterol synthesis and turnover by approximately 40%, but increased significantly the fractional and mass absorption of cholesterol. In accordance with the fecal data, the ratios of the precursor sterols to cholesterol were reduced (-50%), but those of squalene (+48%) and the absorption sterols increased (e.g. 2.6-fold for sitosterol) similarly in each lipoprotein, but progressively from VLDL to HDL.
Effective lowering of LDL cholesterol by large dose of statin is associated with decreased synthesis and turnover of cholesterol and increased fractional and mass absorption of cholesterol. These changes are detectable by noncholesterol sterols in serum and in different lipoprotein fractions.
血清中含有非胆固醇甾醇，它们是胆固醇代谢的可靠标志物，但它们在不同脂蛋白中的存在情况及重要性尚未得到充分研究。
采用甾醇平衡技术，在基线期以及2型糖尿病男性患者接受6个月阿托伐他汀（80毫克/天）治疗期间，对血清和脂蛋白胆固醇前体角鲨烯、胆甾烷醇、羊毛甾醇和谷甾醇（胆固醇合成标志物）以及胆甾烷醇和植物甾醇（胆固醇吸收标志物）、胆固醇的吸收效率和绝对合成量进行了研究。
在基线期，约14%的血清角鲨烯由极低密度脂蛋白（VLDL）转运，12%由中间密度脂蛋白（IDL）转运，40%由低密度脂蛋白（LDL）转运，30%由高密度脂蛋白（HDL）转运。非胆固醇甾醇各自的相应比例约为8%、4%、61%和26%。角鲨烯与胆固醇的比值在VLDL和IDL中最高，胆甾烷醇、羊毛甾醇和吸收标志物甾醇的比值逐渐升高，而从VLDL到HDL，谷甾醇的比值降低。阿托伐他汀使LDL胆固醇降低约50%，使胆固醇的绝对合成和周转率降低约40%，但显著增加了胆固醇的分数吸收和质量吸收。与粪便数据一致，各脂蛋白中前体甾醇与胆固醇的比值降低（-50%），但角鲨烯的比值升高（+48%），吸收甾醇的比值升高（如植物甾醇升高2.6倍），且从VLDL到HDL呈逐渐升高趋势。
大剂量他汀类药物有效降低LDL胆固醇与胆固醇合成和周转率降低以及胆固醇分数吸收和质量吸收增加有关。血清和不同脂蛋白组分中的非胆固醇甾醇可检测到这些变化。
