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)药物对肝脏再生的调节-对肝移植中小体积移植物的有益效果i）草药Inchin-ko-to对大鼠肝切除术后肝功能和再生的有益效果。ICKT组的存活期显着延长。ICKT组术后早期转氨酶、TBA、T-Bil水平明显改善。ICKT组术后残肝/体重比明显增加。在ICKT组中，PCNA和HO-1在术后早期强烈表达，但α-SMA的表达较弱。ii）大面积肝切除术后环孢素A的药代动力学：活体供肝移植中小体积移植物的提示关于CyA的血液浓度，除了Hx后72小时外，在30%和10%移植物模型之间没有差异。至于肝再生，没有发现显著差异。关于表达 ...更多信息 3A 2，在30%移植物模型中没有观察到变化，另一方面，CYP 3A 2表达降低。肝切除后48和72小时，30%和10%移植模型之间观察到显著差异。氟伐他汀对大鼠肝缺血再灌注损伤的保护作用氟伐他汀可减轻再灌注后6小时肝细胞的损伤（p<0.05）。氟伐他汀组eNOS mRNA表达明显高于对照组，而NOX 4 mRNA表达明显低于对照组（p<0.05）。此外，氟伐他汀组的炎症细胞因子mRNA的表达受到抑制。特别是，TNF-α在氟伐他汀组中显著降低（p<0.05）。本研究表明，术前给予氟伐他汀对大鼠肝脏I/R损伤具有有益作用。(2)高压氧预处理对大鼠肝大部切除模型的保护作用HBO-3D组大鼠肝组织HSP 70 mRNA表达较HBO（-）组显著增加（P<0.05）。HBO-3D组HSP 70和HO-1阳性肝细胞数较HBO（-）组明显增多（P<0.05）。70% Hx-HBO组和90%Hx-HBO组的转氨酶均较单纯Hx组显著降低（P<0.05）。术后24、48、72 h，90%Hx-HBO组Lw/Bw比值较90%Hx组显著升高（P<0.05）。90%Hx-HBO组生存率明显高于90%Hx组（P=0.01）。高压氧预处理对大鼠大面积肝切除模型的保护作用可能与诱导HSP 70和HO-1的表达有关。(3)脾切除对大鼠肝大部切除术后肝功能和肝再生的影响：Hx+Sp组大鼠7天生存率为60%，明显高于对照组的18.2%（p<0.05）。肝切除术后48 h，Hx+Sp组ALT和总胆红素迅速下降，差异有统计学意义（P < 0. 05）。肝切除术后的残肝/体重比在任何时间点均无显著差异。术后48、72小时Hx+Sp组PCNA标记指数均高于对照组。脾切除可促进肝大部切除术后肝细胞增殖，改善肝功能，提高生存率。脾切除术被认为是有益的，以改善在大规模肝切除术，这是一个小尺寸移植模型在LDALT的结果。少

项目成果

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

Pharmacokinetics of Cyclosporine A After Massive Hepatectomy : A Hint for Small-for-Size Graft in Living Donor Liver Transplantation

大规模肝切除术后环孢素 A 的药代动力学：活体肝移植中小型移植物的提示

• 发表时间: 2007
• 期刊: Dig Dis Sci 52(10)
• 作者: Shinohara;H
• 通讯作者: H

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