The abnormal lipoprotein (LP-X) observed in cholestasis was deviled into two subfractions (LP-X
1 and LP-X
2) 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-X
1 appeared in plasma 24hrs after ligation of the common bile duct, whereas LP-X
2 also appeared 48hrs after ligation. Seventy-two hours after the ligation, LP-X
1 was found to be higher than LP-X
2.
On the other hand, LP-X
2 was exclusively observed in rats treated with ANIT.
In percentage composition of protein and lipid, LP-X
1 and LP-X
2 were composed of mainly phospholipid and free cholesterol; in particular, the cholesterol ester ratio of LP-X
2 was extremely low in the ANIT treated group.
As to composition of apoproteins, LP-X
2 was abundant in Apo E, which was not detectable in LP-X
1 fraction.
In electron micrographs negatively stained, both LP-X
1 and LP-X
2 showed to be disc-like in shape. In addition, LP-X
1 tended to be larger than LP-X
2 in size.
In summary, LP-X
1 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-X
2 in plasma, since Apo E is exclusively synthesized in the liver.
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