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）对肝脏移植中小晶粒的肝脏再生 - 益生作用的医学调节）草药inchin-ko-to的有益作用，对大鼠肝术后肝功能和再生的有益作用。在ICKT组中，生存期显着延长。在体验后早期，ICKT组的转氨酶和TBA水平显着提高。 ICKT组残留的肝脏/体重比已经显着增加。在ICKT组中，PCNA和HO-1在大规模肝术后的Cyclosporine A的药代动力学A的表达很弱。至于肝脏再生，没有明显的差异。关于CYP的表达…更多3A2，另一方面，在30％的晶粒模型中没有注意到CYP3A2表达降低。肝切开术在30％至10％的谷物模型之间观察到48和72小时的显着差异。 CYA的血液浓度不依赖于肝脏晶粒的体积。III）氟伐他汀对Ratsfluvastatin中肝缺血 - 再灌注损伤的有益作用可减少I/R诱导的肝细胞损伤，6小时后6小时后（P <0.05）。在Fluvastatin组中，eNOS mRNA的表达显着更高，NOX4 mRNA明显低（p <0.05）比对照组中。此外，在Fluvastatin组中抑制了炎性细胞因子mRNA的表达。特别是，fluvastatin组的TNF-___________________________________________________________________________________________________________________________________________________________________________________________________________。这项研究表明，术前施用氟伐他蛋白对大鼠的肝I/R损伤具有有益作用。（2）与HBO（-P <0.05）相比，HBO-3D组的HBO-3D组HBO-3D组对HSP70 mRNA的大规模肝术模型的有益作用显着增加了HBO-3D组的表达。与HBO（ - ）组相比，HBO-3D组的HSP70和HO-1阳性肝细胞显着增加（p <0.05）。与单独的HX组相比，在70％和90％HX-HBO组中的跨力显着降低（p <0.05）。 90％HX-HBO组的LW/BW比显着增加了90％HX组，而HX组24、48和72小时的LW/BW组在肝切开术后的90％组（P <0.05）。 90％HX-HBO组的存活率显着提高，比90％HX组的生存率提高（p = 0.01）。 HBO预处理在大鼠中通过HSP70和HO-1的诱导在大鼠中具有有益的作用。（3）脾切除术对老鼠大规模肝术后肝功能和肝脏再生的影响。与对照组相比，HX+SP组在HX+SP组中提高了外神经菌率（60％VS 18.2％，ps 18.2％，p <0.05）。在HX+SP组中，ALT和总胆红素在肝切开术后48小时迅速改善。肝切开术后残留的肝脏/体重比在任何时间点都没有显着差异。 HX+SP组的肝术后PCNA标记指数48和72小时高于对照组。脾切除术在大规模的肝切开术后促进了肝细胞增殖，并提高了肝功能和存活率。脾切除术被认为有益于改善大规模肝术中的结果，这是LDALT中的小型移植模型。较少的

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