The effect of denervation on liver regeneration in partially hepatectomized rats.
OBJECTIVE
In a partial liver transplantation, the dissected hepatic nerves are left unrepaired during active liver regeneration. In fact, the pathophysiological influence of such hepatic denervation on liver regeneration has not yet been fully clarified. The aim of the present study is to elucidate the effect of total hepatic denervation on liver regeneration.


METHODS
Experiment 1: To confirm the effect of hepatic denervation, the hepatic contents of norepinephrine were measured in both denervated (n = 5) and sham (n = 5) rats. The changes in the hepatic microcirculation were also measured in both denervated (n = 5) and sham (n = 5) rats. Experiment 2: The rats (n = 80) were randomly assigned to two groups: DN group (n = 40); hepatic denervation followed by a partial hepatectomy (PH). Control group (n = 40); sham hepatic denervation followed by PH. In both groups, the animals were killed at 12, 24, 36, 48, 72, 120, and 168 h after PH, respectively. The liver to body weight ratio and the proliferating cell nuclear antigen (PCNA) labeling index were measured at each time point.


RESULTS
Experiment 1: Nearly a total depletion of norepinephrine (<99%) was observed in the DN rats. In addition, the hepatic tissue blood flow significantly increased in the DN rats. Experiment 2: The liver to body weight ratio of the DN group was also significantly higher than that of the control group at 168 h (P < 0.05). The PCNA labeling index peaked between 24 and 36 h in the control group, while that in the DN group showed a delayed peak. At 72 and 120 h, the PCNA labeling index was significantly higher in the DN group than in the control group (P < 0.05).


CONCLUSIONS
Total hepatic denervation was thus found to enhance liver regeneration after a partial hepatectomy. This phenomenon is partially triggered by the increased hepatic blood flow to the remnant liver.
Hamada
Takayuki
T
Department of Transplantation and Digestive Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. takahamada-gi@umin.ac.jp
Eguchi
Susumu
S
Yanaga
Katsuhiko
K
Inuo
Hiroyuki
H
Yamanouchi
Kosho
K
Kamohara
Yukio
Y
Okudaira
Sadayuki
S
Tajima
Yoshitsugu
Y
Kanematsu
Takashi
T
D000818:Animals; D001835:Body Weight / Q000502:physiology; D049109:Cell Proliferation; D003714:Denervation; D006498:Hepatectomy / Q000379:methods*; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000098:blood supply / Q000294:innervation* / Q000601:surgery*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008940:Mitotic Index; D009638:Norepinephrine / Q000378:metabolism; D009929:Organ Size / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology
D018809:Proliferating Cell Nuclear Antigen; D009638:Norepinephrine