Splenectomy enhances liver regeneration through tumor necrosis factor (TNF)-alpha following dimethylnitrosamine-induced cirrhotic rat model.
OBJECTIVE
We demonstrated that partial splenic embolization for hematological disorders in cirrhotic patients also improved liver function. Therefore, we investigated the mechanism of the beneficial effects of splenectomy on a rat cirrhotic model.


METHODS
1) Rats were administered DMN (dimethylnitrosamine) after splenectomy (splenectomized DMN rats) or a sham operation (DMN rats). 2) After completion of DMN administration, a tumor necrosis factor-alpha inhibitor (E3330) was administered on the same day as the splenectomy. Histological examination and cytokine expressions were analyzed.


RESULTS
The splenectomy apparently reduced liver damage. This may be partially due to the enhancement of liver regeneration since the proliferating cell nuclear antigen labeling index in the DMN-treated liver was significantly increased by splenectomy. Tumor necrosis factor-alpha was down-regulated in the DMN rats, whereas its expression was preserved in the splenectomized DMN rats. There were no apparent differences in the number of Kupffer cells between the splenectomized DMN and the DMN rats, suggesting that the down-regulation of tumor necrosis factor-alpha may contribute to the reduction of Kupffer cells' function. In addition, a tumor necrosis factor-alpha production inhibitor (E3330) significantly reduced the proliferating cell nuclear antigen labeling index after splenectomy.


CONCLUSIONS
Splenectomy, in this model, may promote liver regeneration by preserving Kupffer cell function, especially the secretion of tumor necrosis factor-alpha.
Murata
K
K
First Department of Internal Medicine, Mie University School of Medicine, 2-174, Edobashi, Tsu, Mie, Japan.
Shiraki
K
K
Sugimoto
K
K
Takase
K
K
Nakano
T
T
Furusaka
A
A
Tameda
Y
Y
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008115:Liver Regeneration; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013156:Splenectomy; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D016227:Benzoquinones; D011422:Propionates; D014409:Tumor Necrosis Factor-alpha; C075569:E 3330