Role of transforming growth factor-beta1 (TGF-beta1) in endotoxin-induced hepatic failure after extensive hepatectomy in rats.
Postoperative infections after hepatectomy sometimes lead to fatal hepatic failure, but the mechanism of the hepatic failure is unclear. Wistar rats underwent 90% hepatectomy, and were then divided into three groups: (i) the SAL group, injected with normal saline; (ii) the LPS group, injected with lipopolysaccharide (LPS) every day for 1 week; and (iii) the LPS plus TGF-Ab (LPS+TGF-Ab) group, injected with LPS with anti-transforming growth factor-beta1 (TGF-beta1) antibody. We investigated survival rates, TGF-beta1 expression in the liver, liver regeneration by proliferating cell nuclear antigen labeling index, hepatocyte apoptosis by single stranded DNA labeling index, and perisinusoidal fibrosis using Masson's trichrome staining. The LPS group (30.4%) had a significantly lower survival rate than the SAL group (84%) and tended to be lower than the LPS+TGF-Ab group (49.4%). Liver regeneration in the LPS group was significantly lower than in the other groups. In the LPS group, hepatocyte apoptosis and perisinusoidal fibrosis was significantly more remarkable, and TGF-beta1 expression was significantly higher than in the SAL group. TGF-beta1 enhanced by LPS plays an important role in the mechanism of hepatic failure by infections after hepatectomy, especially in inhibition of liver regeneration, and induction of hepatocyte apoptosis and perisinusoidal fibrosis.
Yoshimoto
Noboru
N
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan. yosinobo@isis.ocn.ne.jp
Togo
Shinji
S
Kubota
Toru
T
Kamimukai
Nobuyuki
N
Saito
Shuji
S
Nagano
Yasuhiko
Y
Endo
Itaru
I
Sekido
Hitoshi
H
Nagashima
Yoji
Y
Shimada
Hiroshi
H
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001663:Bilirubin / Q000097:blood; D004731:Endotoxins / Q000494:pharmacology*; D005355:Fibrosis / Q000473:pathology; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006820:Hyaluronic Acid / Q000097:blood; D007150:Immunohistochemistry; D017093:Liver Failure / Q000139:chemically induced* / Q000401:mortality / Q000473:pathology; D008115:Liver Regeneration; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D004731:Endotoxins; D018809:Proliferating Cell Nuclear Antigen; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D006820:Hyaluronic Acid; D000410:Alanine Transaminase; D001663:Bilirubin