脳卒中易発性高血圧自然発症ラット(SHRSP)の高脂肪・高コレステロール食による飼育

リポおよびアポ蛋白の動態

抄録

Studies on serum lipo- and apo-proteins have rapidly progressed in recent years since epidemiologic studies demonstrated that there is a negative correlation between the concentration of high density lipoprotein-cholesterol (HDL-cholesterol) and the occurrence of coronary heart disease, and that HDL, especially HDL2, is an anti-atherogenic factor.
On one hand, the stroke-prone spontaneously hypertensive rat (SHRSP) which was established in 1974, develops arterial fat deposition by high-fat and -cholesterol (HFC) feeding, and is suggested as a useful model for studies on atherosclerosis.
In this report, we investigated 1) serum lipo- and apo-proteins in male SHRSP in comparison with those in age-matched male Kyo: Wistar rat (WKY), and 2) alterations of serum lipo- and apo-proteins in both strains by HFC feeding. In particular, alterations of HDL subfractions were examined by Heparin-Sepharose 4B affinity chromatography.
First, various lipoproteins were fractionated from rat serum by density gradient ultracentrifugation, followed by characterization with various polyacrylamide gel electrophoreses. Next, HDL fraction was subfractionated into two distinct subclasses, HDL rich in apoprotein A-I (Apo A-I HDL) and HDL rich in apoprotein E (Apo E HDL), by Heparin-Sepharose 4B affinity chromatography.
We noticed that the content of Apo E HDL including HDL1 in SHRSP was much lower than that in WKY, which was associated with lower content of Apo E in low density lipoprotein- (LDL-) and HDL-fractions of SHRSP. But, it remains to be determined whether the decreased content of Apo E HDL in SHRSP is due to genetic factors or the secondary effects of hypertension.
In WKY on HFC diet, there was a decrease of Apo E HDL associated with a decrease of Apo E in HDL fraction and an increase of both Apo E and Apo B in LDL- and very low density lipoprotein-(VLDL-) fractions. In SHRSP on HFC diet, the changes were more drastic than those in WKY. Not only Apo E HDL but also Apo A-I HDL decreased, wchich was associated with a decrease of both Apo E and Apo A-I in HDL fraction and a small increase of Apo E and large increase of Apo B in LDL- and VLDL-fractions. These remarkable changes of lipo- and apo-proteins in SHRSP resulted in the decrease of total HDL and the rapid elevation of serum total cholesterol, which could induce the development of arterial fat deposition.