L-精氨酸对大鼠胰腺移植缺血再灌注损伤保护作用及其机制.docVIP

L-精氨酸对大鼠胰腺移植缺血再灌注损伤保护作用及其机制 　 作者：陈 浩1，李寿柏2，程韵枫3，胡伟明4，田伯乐4，张肇达 【摘要】 目的 探讨L-精氨酸 (L-Arginine，L-Arg)对大鼠胰腺移植缺血再灌注(I/R)损伤的影响及其机制。方法 SD大鼠作为供、受体行胰腺移植术，给予不同方式处理：假手术组(Sham)：只行开腹术；对照组(Control)：只行胰腺移植术，不行预处理；缺血预处理组(IPC)：在供胰切取前阻断血供10min，然后再灌注10min；L-精氨酸组(L-Arg)：行胰腺移植术，再灌注前先经下腔静脉注射L-Arg 10mg/kg体重；L-硝基精氨酸甲酯组(L-NAME)：供胰切取时阻断血供10min，再灌注10min；然后行移植术，在再灌注前，先经下腔静脉缓慢注射L-NAME 10mg/kg体重。各组手术完成后，于再灌注6h检测血清淀粉酶、肿瘤坏死因子-α(TNF-α)和一氧化氮(NO)水平，胰腺细胞凋亡指数、胰腺细胞bcl-2蛋白表达情况和胰腺组织病理改变。结果 L-Arg和IPC都降低TNF-α水平(Plt;0.01)和细胞凋亡水平(Plt;0.01)，NO水平升高(Plt;0.01)。而L-NAME可阻断该保护效应。IPC和L-Arg均能激活bcl-2蛋白的表达。结论 L-Arg可以模拟IPC对大鼠胰腺移植I/R损伤的保护作用，其机制与合成NO，激活bcl-2基因的表达有关。 【关键词】 缺血；再灌注损伤；胰腺移植；一氧化氮 【Abstract】 Objective To study the protective effect of L-Arginine on ischemia reperfusion (I/R) injury associated with rat pancreas transplantation and to define a possible mechanism.Methods On the model of pancreas transplantation， male SD rats were randomly assigned to five groups (20 rats in each group)： Sham group(S)： laparotomy only； Control group(C)： pancreas transplantation only； IPC group： donor pancreas underwent ischemic preconditioning (IPC) procedure (10-min ischemia and 10-min reperfusion) before harvest and transplant；L-Arginine group： L-Arg (10mg/kg) was injected into recipient animal via inferior vena cava before transplant； L-NAME group： donor pancreas underwent (IPC) procedure (10-min ischemia and 10-min reperfusion) before harvest and L-NAME (10mg/kg) was injected into recipient animal via inferior vena cava before transplant. Serum amylase， tumor necrosis factor-α(TNF-α) and nitric oxide (NO) levels， apoptosis index of pancreas cells， bcl-2 protein and pancreatic pathological changes were determined 6 h after the operation was completed.Results The significantly decreased values of TNF-α and pancreas cells apoptosis levels but significantly increased NO content showed that L-arginine preconditioning can simulates the protective effects of IPC against I/R injury associated with pancreas transplantation， L-NAME can