|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1999 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1998 : ¥2,600,000 (Direct Cost : ¥2,600,000)
This study was. undertaken to clarify factors modulating lipid composition of bile canalicular membrane in association with hepatic cytoprotection. Especially the pathophysiological significance of phospholipid (PL) species in membrane fluidity and various ATP-binding transporting protein function was focused. For these purposes, intra- and extra-hepatic cholestasis models were prepared by bile duet ligation and phalloidin administration, followed by canalicular membrane vesicle (CMV) preparation in Sprague-Dawley rats. The lipid analyses including phospholipid fatty acide species of CMV by capillary gas- liquid chromatography showed that the cholesterol/phospholipid ratio and saturated/unsaturated fatty acids ratio increased under cholestasis. In contrast, reciprocal changes were evident in sinusoidal membrane -lipid composition and canalicular membrane, sphingomyelin faty acids. On the other hand, the CMV fluidity estimated by DPH polarization was reduced in cholestatic rats, in association with an increased fluidity of sinusoidal membrane vesicles (SMV). Further, all ABC transporter except for Mdr1a and 1b were unchanged. Taken together, the following conclusions are seemingly drawn ; 1) The increased SMV fluidity would be a rescue for preventing biliary constituent accumulation in the liver under cholestasis. 2) The reciprocal changes found in plasma membrane composion suggest that homeostatic mechanisms are seemingly present to some extent in hepatocytes. 3) Further, Mdr1 overexpression may compensate the reduction in biliary component transporters at canalicular membranes as a cytoprotective mechanism.