Bell F P, Hubert E V
Lipids. 1982 Oct;17(10):672-5. doi: 10.1007/BF02534649.
The effect of chlorpromazine, a major tranquilizer, on arterial lipid metabolism was studied in vitro in rat aortas incubated with [14C]acetate and [14C]mevalonate as lipid precursors. Chlorpromazine at a level of 0.25 mM in the incubation medium significantly reduced the incorporation of [14C]acetate into free fatty acids (p less than 0.01) and total phospholipids (p less than 0.001) but not triglycerides. Chlorpromazine also altered the pattern of arterial phospholipids synthesized from [14C]acetate by significantly increasing the relative proportion of phosphatidylinositol plus phosphatidylserine (p less than 0.02) and reducing the relative proportion of sphingomyelin (p less than 0.001). [14C] Acetate incorporation into the combined fractions of steryl esters plus hydrocarbons and sterols plus diglycerides was also significantly reduced (p less than 0.001) by 0.25 mM chlorpromazine. Studies with [14C]mevalonate showed that chlorpromazine is also an inhibitor of sterol biosynthesis in arterial tissues as evidenced by 35-40% reductions (p less than 0.05) in the formation of 14C-labeled squalene and C27 sterols.
以[14C]乙酸盐和[14C]甲羟戊酸作为脂质前体，在体外对大鼠主动脉进行孵育，研究了主要镇静剂氯丙嗪对动脉脂质代谢的影响。孵育培养基中氯丙嗪浓度为0.25 mM时，可显著降低[14C]乙酸盐掺入游离脂肪酸（p<0.01）和总磷脂（p<0.001）的量，但对甘油三酯无影响。氯丙嗪还改变了由[14C]乙酸盐合成的动脉磷脂模式，显著增加了磷脂酰肌醇加磷脂酰丝氨酸的相对比例（p<0.02），并降低了鞘磷脂的相对比例（p<0.001）。0.25 mM氯丙嗪也显著降低了[14C]乙酸盐掺入甾醇酯加烃类以及甾醇加甘油二酯的混合组分中的量（p<0.001）。用[14C]甲羟戊酸进行的研究表明，氯丙嗪也是动脉组织中甾醇生物合成的抑制剂，14C标记的角鲨烯和C27甾醇形成减少35 - 40%（p<0.05）即证明了这一点。
