Zhang Yi, Ye Qi-Fa, Lu Li, Xu Xian-Lin, Ming Ying-Zi, Xiao Jian-Sheng
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Hepatobiliary Pancreat Dis Int. 2005 May;4(2):207-12.
Ischemia/reperfusion (I/R) injury is a major cause of primary graft dysfunction and renders an allograft more immunogenic in orthotopic liver transplantation (OLT). Panax notoginseng saponins (PNS) has been reported to exert protective effects against I/R injury to various organs. The objective of this study is to investigate whether PNS preconditioning protects rat liver grafts from I/R injury via an antiapoptotic pathway.
Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation (OLT) and were divided into PNS preconditioning group(group P) and normal saline control group (group N) randomly according to whether PNS (50 mg/kg) was injected intravenously 1 hour before liver grafts harvesting, and sham group (group S). The animals were separately killed 2, 6 and 24 hours after reperfusion. Plasma samples were collected for test of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Liver tissues were collected to detect histological changes, apoptosis and the expression of TNF-alpha, Bcl-2 and Caspase-3 mRNA.
The serum levels of ALT and AST and the apoptosis index (AI) of liver tissue in group P were lower than in group N significantly 2, 6 and 24 hours after reperfusion. Compared with group N, the expression of TNF-alpha and Caspase-3 mRNA was reduced significantly in group P 2 and 6 hours after reperfusion and the expression of Bcl-2 mRNA was enhanced significantly in group P 6 and 24 hours after reperfusion.
PNS preconditioning protects liver grafts from I/R injury effectively in rat OLT via an antiapoptotic pathway. The antiapoptotic mechanisms of PNS may include inhibiting the expression of TNF-alpha and Caspase-3 and enhancing the expression of Bcl-2.
缺血/再灌注（I/R）损伤是原位肝移植（OLT）中导致原发性移植物功能障碍的主要原因，并且会使同种异体移植物更具免疫原性。据报道，三七总皂苷（PNS）对各种器官的I/R损伤具有保护作用。本研究的目的是探讨PNS预处理是否通过抗凋亡途径保护大鼠肝移植免受I/R损伤。
雄性Sprague-Dawley大鼠作为原位肝移植（OLT）的供体和受体，根据在肝移植获取前1小时是否静脉注射PNS（50mg/kg）随机分为PNS预处理组（P组）和生理盐水对照组（N组），以及假手术组（S组）。再灌注后2、6和24小时分别处死动物。收集血浆样本检测丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）。收集肝组织检测组织学变化、细胞凋亡以及肿瘤坏死因子-α（TNF-α）、Bcl-2和半胱天冬酶-3（Caspase-3）mRNA的表达。
再灌注后2、6和24小时，P组血清ALT和AST水平以及肝组织凋亡指数（AI）均显著低于N组。与N组相比，再灌注后2和6小时P组TNF-α和Caspase-3 mRNA的表达显著降低，再灌注后6和24小时P组Bcl-2 mRNA的表达显著增强。
在大鼠OLT中，PNS预处理通过抗凋亡途径有效保护肝移植免受I/R损伤。PNS的抗凋亡机制可能包括抑制TNF-α和Caspase-3的表达以及增强Bcl-2的表达。
