Improvement of outcome after fatty liver transplantation

脂肪肝移植术后预后的改善

• 批准号: 13671229
• 负责人: HAYASHI Michihiro
• 金额: $ 2.24万
• 依托单位: Osaka Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671229/
• 关键词: liver transplantation; fatty liver; Hepatocyte Growth Factor(HGF); choline-methionine-deficient diet; apoptosis; liver regeneration; preservation-reperfusion injury; cold presrvation; 肝移植; 実験的脂肪肝; グラフトviability; HGF; 脂肪肝グラフト

Transplantation of livers with severe steatosis may result, in primary nonfunction of the grafts. Protective strategies are very rare to safely expand the donor pool to fatty liver. Hepatocyte Growth Factor (HGF) is known as the most potent mitogen for hepatocytes and has been shown to have protective effect and stimulate regeneration in injured livers. Here we examined the effects of human recombinant HGF (hrHGF) on function and survival of preserved fatty liver transplantation. Fatty livers obtained from choline-methionine-deficient diet -fed rats were orthotopically transplanted in normal rats after 12-hour cold preservation. In the HGF group, donor rats were pretreated with hrHGF, and hrHGF was also added to the preservation solution. Twelve hours after hrHGF injection, lipid analyses demonstrated increased serum levels of triglyceride, total cholesterol, low density lipoprotein and very low density lipoprotein. Recipient rat survival was significantly increased in hrHGF-pretreated group compared with control. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels in the effluent before graft revascularization and serum ALT, LDH and HA at 2 hour after reperfusion were significantly low in FLGF group, accompanied with increased hyaluronic acid uptake rate. Pretreatment with hrHGF also significantly reduced the TUNEL positive cells and increased BrdU positive hepatocytes at 2 hour after reperfusion. Sinusoidal endothelial cells (SECs) damage and hepatocyte apoptosis were more severe in control group observed by transmission electron microscope. In conclusion, hrHGF has both protective effects on hepatocytes and SECs at fatty liver transplantation. It inhibited apoptosis of fatty liver during preservation reperfusion injury and induced graft regeneration at early stage after transplantation. Also it might lead to recovery of steatosis by increasing secretion of lipids out of liver.

严重脂肪变性的肝脏移植可能导致移植物原发性无功能。保护性策略非常罕见，可以安全地将供体库扩大到脂肪肝。肝细胞生长因子（HGF）是肝细胞最有效的有丝分裂原，已被证明具有保护作用，并刺激损伤肝脏的再生。在这里，我们研究了人重组肝细胞生长因子（hrHGF）对保存脂肪肝移植的功能和生存的影响。从胆碱-蛋氨酸缺乏饮食喂养的大鼠获得的脂肪肝在冷保存12小时后原位移植到正常大鼠体内。肝细胞生长因子组（HGF组），供体大鼠经hrHGF预处理后，在保存液中加入hrHGF。hrHGF注射后12小时，脂质分析显示甘油三酯、总胆固醇、低密度脂蛋白和极低密度脂蛋白的血清水平升高。与对照组相比，hrHGF预处理组受体大鼠的生存率显着增加。FLGF组血运重建前流出液中AST、ALT和LDH水平及再灌注后2 h血清ALT、LDH和HA水平均显著降低，透明质酸摄取率升高。再灌注后2小时，hrHGF预处理也显著减少TUNEL阳性细胞，增加BrdU阳性肝细胞。透射电子显微镜观察对照组肝窦内皮细胞（SEC）损伤和肝细胞凋亡较严重。总之，hrHGF对脂肪肝移植中的肝细胞和SEC具有保护作用。抑制脂肪肝保存再灌注损伤中的细胞凋亡，并在移植后早期诱导移植肝再生。它也可能通过增加肝脏的脂质分泌而导致脂肪变性的恢复。

项目成果

Michihiro Hayashi: "Current strategies for the use of sub-optimal grafts in living-donor liver transplantation"TRANSPLANTATION PROCEEDINGS. 34(7). 2567-2568 (2001)

Michihiro Hayashi：“活体肝移植中使用次优移植物的当前策略”移植程序。