Oral administration of polyamines ameliorates liver ischemia/reperfusion injury and promotes liver regeneration in rats
Oral administration of polyamines ameliorates liver ischemia/reperfusion injury and promotes liver regeneration in rats
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DOI：
10.1002/lt.24471
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发表时间：
2016-09-01
影响因子：
4.6
通讯作者：
Uemoto, Shinji
中科院分区：
文献类型：
--
作者：
Okumura, Shinya;Teratani, Takumi;Uemoto, Shinji
多胺是细胞生长和分化所必需的。它们在保护肝损伤和促进肝再生方面发挥重要作用。然而，关于口服外源性多胺对肝损伤和再生的影响知之甚少。本研究探讨了多胺（亚精胺和精胺）对缺血/再灌注损伤（IRI）和肝再生的影响。我们使用了一种大鼠模型，其中缺血40分钟后进行70%的肝切除，以模拟活体供者部分肝移植（LT）的临床条件。雄性刘易斯大鼠分为两组：多胺组在手术前后给予多胺作为治疗，溶剂组给予蒸馏水作为安慰剂。多胺组再灌注后6、24和48小时血清天冬氨酸氨基转移酶和丙氨酸氨基转移酶水平显著低于溶剂组。再灌注后6小时，多胺治疗降低了几种促炎细胞因子和趋化因子的表达。组织学分析显示，多胺组在再灌注后6小时的坏死和凋亡明显减少。多胺组窦状隙内皮细胞保存良好。多胺组再灌注后24、48、168 h的残肝再生明显加快，再灌注后24 h的Ki-67标记指数、增殖细胞核抗原和磷酸化视网膜母细胞瘤蛋白的表达明显高于溶剂组。总之，围手术期口服多胺管理衰减肝脏IRI和促进肝再生。这可能是一种新的治疗选择，以改善部分LT的结果。肝移植22 1231-1244 2016 AASLD
Polyamines are essential for cell growth and differentiation. They play important roles in protection from liver damage and promotion of liver regeneration. However, little is known about the effect of oral exogenous polyamine administration on liver damage and regeneration. This study investigated the impact of polyamines (spermidine and spermine) on ischemia/reperfusion injury (IRI) and liver regeneration. We used a rat model in which a 70% hepatectomy after 40 minutes of ischemia was performed to mimic the clinical condition of living donor partial liver transplantation (LT). Male Lewis rats were separated into 2 groups: a polyamine group given polyamines before and after operation as treatment and a vehicle group given distilled water as placebo. The levels of serum aspartate aminotransferase and alanine aminotransferase at 6, 24, and 48 hours after reperfusion were significantly lower in the polyamine group compared with those in the vehicle group. Polyamine treatment reduced the expression of several proinflammatory cytokines and chemokines at 6 hours after reperfusion. Histological analysis showed significantly less necrosis and apoptosis in the polyamine group at 6 hours after reperfusion. Sinusoidal endothelial cells were also well preserved in the polyamine group. In addition, the regeneration of the remnant liver at 24, 48, and 168 hours after reperfusion was significantly accelerated, and the Ki-67 labeling index and the expressions of proliferating cell nuclear antigen and phosphorylated retinoblastoma protein at 24 hours after reperfusion were significantly higher in the polyamine group compared with those in the vehicle group. In conclusion, perioperative oral polyamine administration attenuates liver IRI and promotes liver regeneration. It might be a new therapeutic option to improve the outcomes of partial LT. Liver Transplantation 22 1231-1244 2016 AASLD