Boberg K M, Akerlund J E, Björkhem I
Institute of Clinical Biochemistry, University of Oslo, Norway.
Lipids. 1989 Jan;24(1):9-12. doi: 10.1007/BF02535257.
Attempts were made to develop an animal model for phytosterolemia. Infusion of Intralipid containing 0.2% sitosterol in rats gave circulating levels of sitosterol of about 2.5 mmol/l, which is similar to or higher than those present in patients with untreated phytosterolemia. In addition, the infusions gave serum levels of cholesterol nearly twice those obtained in rats infused with Intralipid alone or Intralipid containing 0.2% cholesterol. The hepatic HMG-CoA reductase activity was unaffected or slightly increased by the sitosterol infusions (not statistically significant). The cholesterol 7 alpha-hydroxylase activity was slightly depressed (ca. 30%). In the case of 7 alpha-hydroxylation of endogenous cholesterol, the depression reached statistical significance (p less than 0.05). The microsomal content of sitosterol in the sitosterol-infused rats was about 30% of that of microsomal cholesterol. The effect of sitosterol on 7 alpha-hydroxylation of cholesterol was investigated by incubations of acetone powder of rat liver microsomes with mixtures of cholesterol and sitosterol. Sitosterol mixed with cholesterol to a composition similar to that found in the above microsomal fraction had a depressing effect on 7 alpha-hydroxylation of cholesterol. This degree of depression was of the same magnitude as that found in the sitosterol infusion experiments. The possibility is discussed that the hypercholesterolemia obtained in the beta-sitosterol-infused rats is due to the inhibitory effect of sitosterol on the cholesterol 7 alpha-hydroxylase.
人们尝试建立植物甾醇血症的动物模型。给大鼠输注含0.2%谷甾醇的英脱利匹特后，谷甾醇的循环水平约为2.5 mmol/l，这与未经治疗的植物甾醇血症患者的水平相似或更高。此外，输注使血清胆固醇水平几乎是单独输注英脱利匹特或输注含0.2%胆固醇的英脱利匹特的大鼠的两倍。谷甾醇输注对内源性胆固醇的7α-羟化酶活性无影响或略有增加（无统计学意义）。胆固醇7α-羟化酶活性略有降低（约30%）。就内源性胆固醇的7α-羟化而言，这种降低具有统计学意义（p<0.05）。输注谷甾醇的大鼠微粒体中谷甾醇的含量约为微粒体胆固醇含量的30%。通过将大鼠肝脏微粒体丙酮粉与胆固醇和谷甾醇混合物孵育，研究了谷甾醇对胆固醇7α-羟化的影响。与上述微粒体部分中发现的组成相似的谷甾醇与胆固醇混合后，对胆固醇的7α-羟化有抑制作用。这种抑制程度与在谷甾醇输注实验中发现的程度相同。文中讨论了输注β-谷甾醇的大鼠出现高胆固醇血症可能是由于谷甾醇对胆固醇7α-羟化酶的抑制作用。
