Disorganization of microtubular network in postischemic liver dysfunction: its functional and morphological changes.
Microtubules in the hepatocytes have been implicated to serve as lines of cytoplasmic transport of secretory materials, but are highly labile structures sensitive to pathological conditions in the cytosol. We examined the role of ischemia/reperfusion-induced cytoskeletal alterations in postischemic liver dysfunction. Rabbit livers were subjected to 60-min warm ischemia followed by 1 h or 24 h of reperfusion. Liver function was assessed by directly measuring hepatic clearance of indocyanine green (ICG), an organic anion whose cytoplasmic transport is assumed to depend on intact microtubules, using near-infrared spectroscopy. Structural alterations of microtubules were observed immunohistochemically using tissue sections stained with monoclonal anti-beta-tubulin antibody. ICG removal from hepatocytes into bile canaliculi deteriorated 1 h but reversed 24 h after reperfusion. Immunohistochemistry showed fragmentation of microtubules at the end of liver ischemia. This cytoskeletal alteration was evident 1 h but was not observed 24 h after reperfusion. Treatment with prostaglandin E1 exerted its beneficial effect by preserving ICG clearance and microtubular network. These results demonstrate that liver ischemia and subsequent reperfusion both affect the organization of microtubular network and suggest that structural disruption of microtubules may be a cause of postischemic liver dysfunction.
Shinohara
H
H
Second Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Tanaka
A
A
Fujimoto
T
T
Hatano
E
E
Satoh
S
S
Fujimoto
K
K
Noda
T
T
Ide
C
C
Yamaoka
Y
Y
D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000199:Actins / Q000032:analysis; D000527:Alprostadil / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004396:Coloring Agents / Q000378:metabolism; D007150:Immunohistochemistry; D007208:Indocyanine Green / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism / Q000473:pathology*; D007700:Kinetics; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D013053:Spectrophotometry; D014404:Tubulin / Q000032:analysis
D000199:Actins; D004396:Coloring Agents; D014404:Tubulin; D000527:Alprostadil; D007208:Indocyanine Green