抗動脈硬化剤の作用無機序の研究

Abstract

The development of atherosclerosis is characterized by the focal accumulation of lipid in arterial wall. In this accumulated lipids, the content of cholesterol ester and phospholipid are high and triglyceride is not high. In order to clarify the mechanism contributing to this characteristic lipid content, we have undertaken an investigation of lipid metabolism concerned with cholesterol ester, phospholipid and triglyceride in rat arterial wall. Furthermore, the effect of pantethine, as an antiatherosclerotic agent, on the lipid metabolism was investigated. Male Wistar-King strain rats were fed a normal or a high cholesterol diet with or without pantethine for 4 weeks in the following manner: 1) Normal diet, 2) Normal diet plus pantethine (200mg/day), 3) High cholesterol diet which contains 1% cholesterol-0.5% cholic acid and 4) High cholesterol diet plus pantethine. Increased of acyl-CoA synthesis from palmitate-14C was observed when extracts of rat arterial wall were incubated with pantethine (1mg/ml). Cholesteryl ester synthesis from palmitate-1-14C in the arterial wall slices was higher with arteries from rat on high cholesterol diet than with those from rats on normal diet, but the synthesis was reduced in the arteries of rats on high cholesterol diet with pantethine. Triglyceride synthesis from palmitate-1-14C was higher with arterial wall slices of rats on high cholesterol diet than with preparations from rats on normal diet and was increased with those of rats on high cholesterol diet plus pantethine. Phospholipid synthesis from palmitate-1-14C was higher with arterial wall slices of rats on high cholesterol diet than with those from rats on normal diet and was not reduced with those of rats on high cholesterol diet plus pantethine. From these results, pantethine might possess the preventive action of atherosclerosis by reduction of cholesterol ester synthesis and no reduction of increased phospholipid synthesis.