RRC ID |
42646
|
著者 |
Aihaiti X, Hayamizu K, Oishi K, Yoshimitsu M, Itamoto T, Asahara T.
|
タイトル |
Facilitation of survival in a rat fulminant hepatic failure model by combination therapy using recombinant G-CSF and tacrolimus.
|
ジャーナル |
J Interferon Cytokine Res
|
Abstract |
The mortality rate of fulminant hepatic failure (FHF) is high because of retarded liver regeneration. Recombinant human granulocyte colony-stimulating factor (rHuG-CSF) and tacrolimus are known to be immunosuppressive and supportive to liver regeneration. We investigated the effects of their combination therapy in a rat FHF model with a 68% partial hepatectomy and 24% liver necrosis. All rats without drug pretreatment died within 55 h. The median time was prolonged from 37 to 52 h by rHuG-CSF (250 microg/kg/day s.c. on days -5 to 0) and to 46 h by tacrolimus (0.5 mg/kg/day i.m. on days -2 to 0). Notably, the combination therapy facilitated DNA biosynthesis and survival prolongation, with a median of 77 h. The interferon-gamma (IFN-gamma) protein levels and natural killer cell (NK) activity in the liver were low at 12 h, and no further inhibition was detected by any treatment. Tacrolimus significantly upregulated the mRNA levels of insulin receptors and transforming growth factor-alpha (TGF-alpha), whereas rHuG-CSF did not. Regarding tissue remodeling-related factors, rHuG-CSF upregulated mRNA levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase- 9 (MMP-9), whereas tacrolimus did not. The combination treatment upregulated protein levels of both insulin receptors and VEGF. These results suggest that tacrolimus improves the hepatocyte replication and rHuG-CSF contributes to tissue reconstitution, and this combination therapy directly facilitates liver regeneration in the FHF model.
|
巻・号 |
26(4)
|
ページ |
226-34
|
公開日 |
2006-4-1
|
DOI |
10.1089/jir.2006.26.226
|
PMID |
16704299
|
MeSH |
Animals
DNA Replication / drug effects
Disease Models, Animal
Drug Therapy, Combination
Granulocyte Colony-Stimulating Factor / therapeutic use*
Hepatocytes / drug effects
Hepatocytes / metabolism
Immunosuppressive Agents / therapeutic use*
Interferon-gamma / genetics
Interferon-gamma / metabolism
Killer Cells, Natural / immunology
Liver / drug effects
Liver / immunology
Liver / metabolism
Liver Failure, Acute / drug therapy*
Liver Regeneration*
Male
Matrix Metalloproteinase 9 / genetics
Matrix Metalloproteinase 9 / metabolism
RNA, Messenger / analysis
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Receptor, Insulin / genetics
Receptor, Insulin / metabolism
Recombinant Proteins
Tacrolimus / therapeutic use*
Transforming Growth Factor alpha / genetics
Transforming Growth Factor alpha / metabolism
Treatment Outcome
Up-Regulation
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism
|
IF |
2.032
|
引用数 |
1
|
WOS 分野
|
IMMUNOLOGY
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
YAC-1(RCB1165) |