Bolus Administration of Polyamines Boosts Effects on Hepatic Ischemia-Reperfusion Injury and Regeneration in Rats
Bolus Administration of Polyamines Boosts Effects on Hepatic Ischemia-Reperfusion Injury and Regeneration in Rats
复制标题
DOI：
10.1159/000497434
复制
发表时间：
2019-01-01
影响因子：
1.6
通讯作者：
Uemoto, Shinji
中科院分区：
文献类型：
--
作者：
Doi, Junshi;Fujimoto, Yasuhiro;Uemoto, Shinji
背景：研究表明，多胺可减轻肝脏缺血再灌注损伤（IRI），促进肝脏再生。多胺治疗的最佳方案在临床环境中仍然未知。我们使用大鼠模型检查了2种给药方法。方法：实验一：多胺药代动力学评价。实验二：在术前3天和术后5天，将多胺给予以下三组雄性刘易斯大鼠：对照组，不给予多胺;食物组，在食物中混合0.05%多胺;推注组，通过胃管每天一次给予多胺（200 μ mol/kg）。所有大鼠在40 min的温热IRI后接受70%肝切除术。术后通过测定血清肝酶水平、肝组织病理学和免疫组化以及测量残肝重量来评价IRI和再生情况。结果如下：在门静脉中的多胺的血液浓度增加，在1小时的推注给药，而他们没有增加没有推注。推注组与较低的血清天冬氨酸/丙氨酸转氨酶水平显著相关肝细胞充血、空泡化、坏死程度明显减轻（P < 0.05）（p < 0.05），TUNEL阳性肝细胞的数量较低（p < 0.05），在24、48和168 h时较高的残肝重量（p < 0.05），以及较高的Ki-67标记指数（24 h，p < 0.01）。结论：静脉注射多胺能更有效地改善IRI，促进再生。当临床应用时，围手术期推注多胺可能是最佳治疗方法。
Background:It was demonstrated that polyamines ameliorate ischemia-reperfusion injury (IRI) and promote regeneration in the liver. An optimal protocol of polyamine treatment remains unknown in the clinical setting. We examined 2 types of administration methods using rat models. Methods: Experiment 1: evaluation of pharmacokinetics of polyamines. Experiment 2: for 3 days preoperatively and 5 days postoperatively, polyamines were given to male Lewis rats in the following three groups: the control group, no polyamine administration; the chow group, 0.05% polyamines mixed in chow; the bolus group, polyamines (200 mu mol/kg) given by gastric tube once a day. All rats received 70% hepatectomy after 40 min of warm IRI. Postoperatively, IRI and regeneration were evaluated with assessment of serum levels of hepatic enzymes, histology and immunohistochemistry of liver tissue, and measurement of remnant liver weight. Results: The blood concentrations of polyamines in the portal vein increased at 1 h of bolus administration, while they did not increase without the bolus. The bolus group was significantly associated with lower serum levels of aspartate/alanine aminotransferases (p < 0.05), decreased hepatocyte congestion, vacuolization and necrosis in histopathological scoring (p < 0.05), a lower number of TUNEL-positive hepatocytes (p < 0.05), higher remnant liver weight at 24, 48, and 168 h (p < 0.05), and a higher Ki-67 labeling index (24 h, p < 0.01) compared with the chow group. Conclusion: The bolus administration of polyamines was more effective in ameliorating IRI and promoting regeneration than chow administration. Perioperative bolus administration of polyamines might be an optimal treatment, when clinically applied.