The strategies for overcoming the graft dysfunction after liver transplantation using small-for-size graft

克服小体积肝移植术后移植物功能障碍的策略

• 批准号: 17390370
• 负责人: SHIMADA Mitsuo
• 金额: $ 10.05万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390370/
• 关键词: liver transplantation; small-for-size graft; graft dysfunction; liver regeneration; massive hepatectomy model; heat-shock protein; hyperbaric oxygen; preconditioning

(1) Medical modulation on liver regeneration-Beneficial Effects on small-for-size graft in liver transplantationi) 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 transplantationRegarding 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 … More 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 RatsFluvastatin 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 RatsThe 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

(1)肝脏再生的药物调节——对肝移植中的小尺寸移植物、对大鼠肝切除后的肝功能和再生的有益影响。ICKT组的转氨酶和TBA、T-的存活期显着延长。术后早期ICKT组的胆汁水平显着改善，ICKT组的残余肝脏/体重比显着。在ICKT组中，术后早期PCNA和HO-1表达强烈，但α-SMA表达较弱。ii)大面积肝切除术后环孢素A的药代动力学：活体小尺寸移植物的提示。供体肝移植除了Hx后72小时外，关于CyA的血液浓度，在30％和10％移植模型之间没有发现差异。至于肝再生，没有发现显着差异。关于CYP 3A2的表达，在30%移植模型中没有观察到变化，另一方面，在肝切除后48和72小时，在30%和10%移植模型之间观察到显着差异。 CyA 浓度不依赖于肝移植物的体积。iii) 氟伐他汀对肝缺血再灌注损伤的有益作用大鼠再灌注6小时后氟伐他汀减轻I/R诱导的肝细胞损伤(p<0.05)。氟伐他汀组eNOS mRNA的表达显着高于对照组，NOX4 mRNA的表达显着低于对照组(p<0.05)。此外，氟伐他汀组炎症细胞因子mRNA的表达受到抑制，特别是TNF-_在氟伐他汀组显着降低。 (p<0.05)。本研究证明术前给予氟伐他汀对大鼠肝I/R损伤具有有益作用。(2)高压氧预处理对大鼠大规模肝切除模型的有益作用HBO中HSP70 mRNA的表达显着增加。 -3D组与HBO(-)组相比(P<0.05)，HBO-3D中HSP70和HO-1阳性肝细胞明显增多。与HBO(-)组相比(P<0.05)，70%Hx-HBO组和90%Hx-HBO组的转氨酶均较单独Hx组显着降低(P<0.05)。肝切除后24、48、72小时%Hx-HBO组较90%Hx组显着升高，与90%Hx组相比(P<0.05)。HBO预处理通过诱导HSP70和HO对大鼠大面积肝切除模型的存活率显着提高(P=0.01)。 -1.(3)脾切除对大鼠肝切除术后肝功能及肝再生的影响。Hx+Sp组较对照组存活率提高（7 天，60% vs 18.2%，p<0.05），肝切除后 48 小时，ALT 和总胆红素迅速改善，肝切除后残余肝脏/体重比没有显着差异。 Hx+Sp组肝切除后任意时间点的PCNA标记指数均高于对照组，脾切除后促进肝细胞增殖。肝切除术以及改善肝功能和存活率被认为有利于改善大面积肝切除术的结果，大面积肝切除术是 LDALT 的小型移植模型。

项目成果

生体肝移植における過小グラフトに対する高圧酸素療法の有用性

高压氧治疗在活体肝移植中对尺寸过小的移植物的作用

• 发表时间: 2005
• 期刊: 日本臨床高気圧酸素・潜水医学会雑誌 1
• 作者: 島田光生;藤井正彦;居村 暁;森根裕二;石橋広樹;伊地知秀樹;八木博司
• 通讯作者: 八木博司

New Type of Artificial Liver Support System (ALSS) Using the Photo-catalyst Effect of Titanium Oxide.

利用氧化钛光催化效应的新型人工肝支持系统（ALSS）。

• 期刊: Digestive Diseases and Science (in press)
• 作者: 島田光生;藤井正彦;居村 暁;森根裕二;石橋広樹;伊地知秀樹;八木博司;島田光生;Shinohara H
• 通讯作者: Shinohara H

Liver transplantation for hepatocellular carcinoma

• DOI: 10.1016/b978-0-323-34062-5.00115-1
• 发表时间: 2017
• 期刊: Gastroenterology
• 影响因子: 29.4
• 作者: G. Roll;J. Roberts

門脈再建早期・晩期門脈血栓症とその対策

门静脉重建早期/晚期门静脉血栓及其对策

• 发表时间: 2006
• 期刊: 外科 特集/生体肝移植における門脈・肝静脈再建 68(3)
• 作者: Mizuno S;Yokoi H;Isaji S;Yamagiwa K;Tabata M;Shimono T;Miya F;Takada Y;Uemoto S.;Shimada M;Sugimoto K;島田光生;島田光生;居村暁;居村暁;森根裕二
• 通讯作者: 森根裕二

生体肝移植における過小グラフトの病態生理と治療戦略

活体肝移植移植不足的病理生理学及治疗策略

• 发表时间: 2006
• 期刊: 四国医学会雑誌 62巻1-2
• 作者: Mizuno S;Yokoi H;Isaji S;Yamagiwa K;Tabata M;Shimono T;Miya F;Takada Y;Uemoto S.;Shimada M;Sugimoto K;島田光生
• 通讯作者: 島田光生