摘要
目的探讨Ｌ精氨酸在大鼠原位肝移植冷缺血再灌注损伤过程中对移植肝及肺的功能作用．方法应用同基因Ｗｉｓｔａｒ大鼠原位肝移植（ＯＬＴ）动物模型，６６只大鼠随机分成３组（ｎ＝１１）：Ｌ精氨酸组（ＬＡ）、ＮＯＳ抑制剂组（ＬＮＡＭＥ，ＬＮ）及乳酸钠林格液组（ＬＲ），供肝保存６ｈ再行原位肝移植术．结果大鼠原位肝移植缺血再灌注后血清ＮＯｘ水平及肝组织ｃＧＭＰ水平迅速下降．应用Ｌ精氨酸以加强一氧化氮生物合成途径（ＮＯＳＰ），能显著延长受体的存活率，ＬＲ组受体１ｗｋ存活率为２０％，ＬＡ组为８０％（ｎ＝６，Ｐ＜００１ｖｓＬＲ），并能明显改善肝功能；病理检查示Ｌ精氨酸能维持肝细胞完整性，促进肝再生，而且对再灌注时合并肺损伤也有明显的保护作用．ＮＯＳ抑制剂则能降低术后受体的存活率，加剧肝功能恶化；病理检查示肝内血栓形成，移植肝及肺组织结构严重破坏及更为严重的炎症反应．结论在大鼠原位肝移植缺血再灌注损伤过程中，Ｌ精氨酸器官保存液加强ＮＯ途径（ＮＯＳＰ）将对移植肝及肺具有重要的保护作用．表明ＮＯ合成途径很可能是肝移植器官保存成功的关键因素，从而为加强肝移植器官保存提供了一种新的药理学途径．
AIM To investigate the functional of L arginine in grafted liver and lung during ischemia reperfusion injury (I RI) in rat orthotopic liver transplantation (OLT). METHODS Using a syngeneic Wistar rat orthotopic liver transplantation (OLT) model, 66 rats were randomly divided into three groups ( n =11): L arginine (LA), nitric oxide inhibitor (L NAME, LN) and lactated Ringer's (LR) solution. After 6 hours of preservation, orthotopic implantation of the donor liver was performed. RESULTS Serum nitric oxide and cGMP levels in the grafted liver tissues lowered immediately upon reperfusion in rat orthotopic liver transplantation. L arginine was used to supplement the nitric oxide synthesizing pathway (NOSP), which prolonged the survival of the recipient with a one week survival of 20% for LR and 80% for LA liver ( n =6, 28 8d±36 6d, P <0 01 vs LR), and improved the hepatic function. Histopathology indicated that L arginine can maintain the intergrity of hepatocytes, improve the hepatic regeneration and protect the lung from injury during cold hepatic I RI . In contrast, the grafted liver function and survival were inferior in all cases with inhibited nitric oxide production, resulting in intrahepatic thrombosis, severe destruction of the grafted liver and lung tissues, and more severe inflammatory response of the recipient. CONCLUSION L arginine in a storage solution to supplementing NOSP can protect the grafted liver and the lungs from injury during ischemia reperfusion in orthotopic liver transplantation. The NOSP in liver transplantation may be a critical determinant of successful organ transplantation, thus providing a useful pharmacological approach to enhancing liver preservation.
关键词
精氨酸
药理
肝移植
再灌注损伤
肝
肺
arginine/pharmacology
liver transplantation
nitric oxide/metabolism
reperfusion injury
rats, Wistar
liver/pathology
lung/pathology
