Portal blood flow regulates volume recovery of the rat liver after partial hepatectomy: molecular evaluation.
OBJECTIVE
Liver regeneration is a finely tuned process that is closely regulated by multiple cell cycle steps. Although the portal blood flow affects liver regeneration, the molecular mechanism by which the blood flow regulates gene expression and liver function is largely unknown. The aim of this study was to investigate the molecular effect of portal blood flow on hepatocyte proliferation and gene regulation during liver regeneration.


METHODS
We developed a simple surgical rat model to investigate the relation between portal blood flow and liver regeneration by partially ligating the portal trunk with 8-0 Proline sutures under microscopy to reduce the blood flow by 40%. We investigated recovery of liver volume, DNA synthesis, and gene expression associated with cell cycle regulators, comparing partially hepatectomized (PH) rats without (PH group; n = 30) and with partial portal ligation (PHPL group; n = 30) for 7 days after the operation.


RESULTS
The hepatic tissue blood flow and the recovery ratio between liver weight and body weight in the PHPL group were significantly lower than in the PH group after hepatectomy. The peak 5-bromo-2'-deoxyuridine labeling index in the PHPL group was delayed and weak compared with the PH group. The expression of CT-1 and cyclin D, E, and B mRNAs indicated that the liver regeneration in the PHPL group was delayed and weak. In addition, there was reciprocal expression of C/EBPalpha and C/EBPbeta mRNAs, an observation supported by their nuclear protein levels. Furthermore, the cytochrome P-450 protein level in the PHPL group was higher than that in the PH group 1 day after hepatectomy.


CONCLUSIONS
The portal blood flow regulates the activity of liver regeneration and the gene expression associated with cell cycle regulators, while the functions are maintained.
Nobuoka
T
T
Department of Surgery I, Sapporo Medical University Hospital, Sapporo, Japan.
Mizuguchi
T
T
Oshima
H
H
Shibata
T
T
Kimura
Y
Y
Mitaka
T
T
Katsuramaki
T
T
Hirata
K
K
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics; D016213:Cyclins / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D006498:Hepatectomy; D007150:Immunohistochemistry; D008099:Liver / Q000098:blood supply*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D011168:Portal System / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D016213:Cyclins; D016207:Cytokines; D012333:RNA, Messenger; C092073:cardiotrophin 1; D001973:Bromodeoxyuridine