Milliat F, Férézou J, Delhon A, Lutton C
Laboratoire de physiologie de la nutrition (unité associée à l'Inra), université Paris-Sud, centre d'Orsay, bâtiment 447, 91405 Orsay, France.
C R Acad Sci III. 2001 Mar;324(3):229-34. doi: 10.1016/s0764-4469(00)01299-3.
The effect of a novel acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitor on cholesterol metabolism was studied in hamsters. Oral administration of F12511 (10 mg/kg/d) for 4 weeks produced a decrease in dietary cholesterol absorption (-18%) and in the liver concentration of esterified cholesterol (-75%), as compared with control values in untreated hamsters. While the hepatic expression of LDLr was unchanged by the treatment, that of SR-BI was increased (+142%), which suggests that the hepatic expression of SR-BI could be upregulated by a depletion of the cholesterol stores, due to ACAT inhibition. This SR-BI overexpression, however, did not induce a fall in plasma HDL-cholesterol concentration, in contrast with previous reports in transgenic mice overexpressing SR-BI at a higher extent.
在仓鼠中研究了一种新型酰基辅酶A：胆固醇酰基转移酶（ACAT）抑制剂对胆固醇代谢的影响。与未治疗仓鼠的对照值相比，口服F12511（10mg/kg/天）4周可使膳食胆固醇吸收减少（-18%），肝脏酯化胆固醇浓度降低（-75%）。虽然治疗对肝脏低密度脂蛋白受体（LDLr）的表达没有影响，但清道夫受体B1（SR-BI）的表达增加（+142%），这表明由于ACAT抑制导致胆固醇储存减少，可能会上调肝脏SR-BI的表达。然而，与之前在更高程度过表达SR-BI的转基因小鼠中的报道相反，这种SR-BI的过表达并没有导致血浆高密度脂蛋白胆固醇（HDL-胆固醇）浓度下降。
