2006 Fiscal Year Final Research Report Summary
The strategies for overcoming the graft dysfunction after liver transplantation using small-for-size graft
| Project/Area Number |
17390370
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | The University of Tokushima |
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Principal Investigator |
SHIMADA Mitsuo The University of Tokushima, Institute of Health Biosciences, Professor, 大学院ヘルスバイオサイエンス研究部, 教授 (10216070)
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| Co-Investigator(Kenkyū-buntansha) |
ITAKURA Mitsuo The University of Tokushima, Institute of Health Biosciences, Professor, ゲノム機能研究センター, 教授 (60134227)
SOEJIMA Yuji The University of Tokushima, Institute of Health Biosciences, Part-time lecturer, 大学院ヘルスバイオサイエンス研究部, 非常勤講師 (30325526)
FUJII Masahiko The University of Tokushima, Institute of Health Biosciences, Part-time lecturer, 大学院ヘルスバイオサイエンス研究部, 非常勤講師 (20380040)
IMURA Satoru The University of Tokushima, Institute of Health Biosciences, Assistant professor, 大学院ヘルスバイオサイエンス研究部, 助手 (90380021)
MORINE Yuji Tokushima University, Hospital, Assistant professor, 医学部・歯学部附属病院, 助手 (60398021)
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| Project Period (FY) |
2005 – 2006
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| Keywords | liver transplantation / small-for-size graft / graft dysfunction / liver regeneration / massive hepatectomy model / heat-shock protein / hyperbaric oxygen / preconditioning |
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| Research Abstract |
(1) Medical modulation on liver regeneration-Beneficial Effects on small-for-size graft in liver transplantation
i) Beneficial effects of herbal medicine Inchin-ko-to, on liver function and regeneration after hepatectomy in rats.
The survival period was significantly prolonged in the ICKT group. The transaminase and TBA, T-Bil levels significantly were improved in the ICKT group in the early postoperative period. The remnant liver/body weight ratio in ICKT group had been a significant increase postoperatively. In the ICKT group, PCNA and HO-1 was strongly expressed early postoperatively, but the expression of alpha-SMA was weak.
ii) Pharmacokinetics of Cyclosporine A after massive hepatectomy : A hint for small-for-size graft in living donor liver transplantation
Regarding the blood concentration of CyA, no difference was recognized between 30% and 10% graft model except for 72hrs after Hx. As for liver regeneration, no significant difference was recognized. Regarding the expression of CYP
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3A2, no change was noted in 30% graft model, on the other hand, CYP3A2 expression reduced. Significant differences were observed in 48 and 72 hrs after hepatectomy between 30% and 10% graft model. The blood concentration of CyA was not dependent on the volume of the liver graft.
iii) Beneficial Effects of Fluvastatin on Hepatic Ischemia-Reperfusion Injury in Rats
Fluvastatin reduced the I/R-induced hepatocellular injury at 6hrs after reperfusion (p<0.05). In the fluvastatin group, the expression of eNOS mRNA was significantly higher, and NOX4 mRNA was significantly lower (p<0.05) than in the control group. Furthermore, the expression of inflammatory cytokines mRNA were suppressed in the fluvastatin group. In particular, TNF-_was significantly lower in the fluvastatin group (p<0.05). This study demonstrated that preoperative administration of fluvastatin had beneficial effects on hepatic I/R injury in rats.
(2) Beneficial Effects of Hyperbaric Oxygen Pretreatment on Massive Hepatectomy Model in Rats
The expression of HSP70 mRNA was significantly increased in HBO-3D group compared to HBO (-) group (P<0.05). The HSP70 and HO-1 positive hepatocytes were significantly increased in HBO-3D group compared to HBO (-) group (P<0.05). Transaminases in both 70%-and 90%Hx-HBO group were significantly decreased compared to those of Hx alone group (P<0.05). The Lw/Bw ratio of 90%Hx-HBO group was significantly increased than in 90%Hx group, compared to that of 90%Hx group 24, 48 and 72 hours after hepatectomy (P<0.05). The survival rate in 90%Hx-HBO group was significantly improved than that in 90%Hx group (P=0.01). HBO pretreatment had beneficial effects in massive hepatiectomy model in rats via the induction of HSP70 and HO-1.
(3) Effects of splenectomy on liver function and liver regeneration after massive hepatectomy in rats.
Survival rate was improved in Hx+Sp group compared with control group (7-days, 60% vs 18.2%, p<0.05). In Hx+Sp group, ALT and total bilirubin were quickly improved 48 hours after hepatectomy, significantly. The remnant liver/body weight ratio after hepatectomy was not significantly different at any time points. PCNA labeling index 48 and 72 hours after hepatectomy in Hx+Sp group was higher than that in control group. Splenectomy promoted hepatocyte proliferation after massive hepatectomy, and improved liver function and survival rate. Splenectomy is considered to be beneficial for improving the outcome in massive hepatectomy, which is a small-for-size graft model in LDALT. Less
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