FORMATION OF LP-X SUBFRACTIONS AND ITS UNDERLYING MECHANISM IN EXPERIMENTAL CHOLESTASIS

Abstract

The abnormal lipoprotein (LP-X) observed in cholestasis was deviled into two subfractions (LP-X₁ and LP-X₂) by zonal ultracentrifugation. To elucidate the mechanism of the formation, we utilized the common bile duct ligated-rats as an experimental model for extrahepatic cholestasis and those to which α-naphtylisothiocyanate (ANIT, 200mg/kg body weight) was administered as that for intrahepatic cholestasis.
LP-X₁ appeared in plasma 24hrs after ligation of the common bile duct, whereas LP-X₂ also appeared 48hrs after ligation. Seventy-two hours after the ligation, LP-X₁ was found to be higher than LP-X₂.
On the other hand, LP-X₂ was exclusively observed in rats treated with ANIT.
In percentage composition of protein and lipid, LP-X₁ and LP-X₂ were composed of mainly phospholipid and free cholesterol; in particular, the cholesterol ester ratio of LP-X₂ was extremely low in the ANIT treated group.
As to composition of apoproteins, LP-X₂ was abundant in Apo E, which was not detectable in LP-X₁ fraction.
In electron micrographs negatively stained, both LP-X₁ and LP-X₂ showed to be disc-like in shape. In addition, LP-X₁ tended to be larger than LP-X₂ in size.
In summary, LP-X₁ may well be formed by the regurgitation of the bile components into the circulation, while hepatocyte may play a role, at least partly, in the appearance of LP-X₂ in plasma, since Apo E is exclusively synthesized in the liver.