Effect of Angiotensin II and Bradykinin Inhibition in Rat Reduced-Size Liver Transplantation
Effect of Angiotensin II and Bradykinin Inhibition in Rat Reduced-Size Liver Transplantation
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DOI：
10.1002/lt.21693
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发表时间：
2009-03-01
影响因子：
4.6
通讯作者：
Rosello-Catafau, Joan
中科院分区：
文献类型：
--
作者：
Padrissa-Altes, Susagna;Franco-Gou, Rosa;Rosello-Catafau, Joan
本研究探讨血管紧张素II（Ang II）阻断剂[Ang II I型受体拮抗剂，Ang II II II型受体拮抗剂，血管紧张素转换酶（ACE）抑制剂]是否可以减少肝损伤，改善再生减体积原位肝移植（ROLT）和缺血预处理（PC）在ROLT的有益效果是否可以解释的Ang II的变化。我们发现，小肝移植产生血管紧张素Ⅱ后，ROLT，这是与血管紧张素原和ACE信使RNA表达增加。此外，Ang II的抑制并不有助于PC诱导的ROLT保护。所有的血管紧张素Ⅱ阻断剂都能减轻肝损伤，但都不能促进肝再生。缓激肽（BK）受体拮抗剂促进肝再生，但没有减少肝损伤的ROLT。最后，在ROLT中联合使用Ang II阻断剂和BK受体拮抗剂可减轻肝损伤并改善肝再生。总之，血管紧张素II受体阻滞剂或BK受体拮抗剂的治疗本身不能改善ROLT的结果。虽然血管紧张素Ⅱ阻断剂可以减少肝脏缺血再灌注损伤和BK受体拮抗剂可以促进肝再生，但两者都不能同时带来好处。因此，同时应用这两种治疗可能具有临床意义。肝移植15：313-320，2009。(C)2009年AASLD。
This study examined whether angiotensin II (Ang II) blockers [Ang II type I receptor antagonist, Ang II type II receptor antagonist, and angiotensin converting enzyme (ACE) inhibitor] could reduce hepatic injury and improve regeneration in reduced-size orthotopic liver transplantation (ROLT) and whether the beneficial effects of ischemic preconditioning (PC) in ROLT could be explained by changes in Ang II. We show that small liver grafts generated Ang II after ROLT and that this was associated with increased angiotensinogen and ACE messenger RNA expression. Furthermore, inhibition of Ang II did not contribute to PC-induced protection in ROLT. All Ang II blockers reduced hepatic injury, but none of them promoted liver regeneration. Bradykinin (BK) receptor antagonist improved liver regeneration but did not reduce hepatic injury in ROLT. Finally, the combination of Ang II blockers and BK receptor antagonists in ROLT reduced hepatic injury and improved liver regeneration. In conclusion, treatments with either Ang II blockers or BK receptor antagonists cannot, on their own, improve the outcome of ROLT. Although Ang II blockers can reduce hepatic ischemia-reperfusion injury and BK receptor antagonists can promote liver regeneration, neither confers both benefits at the same time. Consequently, it may be of clinical interest to apply both treatments simultaneously. Liver Transpl 15:313-320, 2009. (C) 2009 AASLD.