去铁胺对自体肝移植大鼠肝脏缺血再灌注损伤的保护作用

目的 探讨去铁胺预处理对大鼠自体肝移植缺血再灌注损伤的保护作用及其可能机制.方法 建立大鼠自体肝移植模型,将96只健康雄性SD大鼠随机分为去铁胺预处理(deferoxamine,D组),注射用水对照组(control group,C组)和假手术模型(shsm operation,S组)各32只.分别于术后0.5 h、2 h、6 h、24 h各时间点处死大鼠,检测血清ALT和AST水平和肝组织SOD活性与MDA含量;做病理组织学检查,免疫组化检测HIF-1α、TNF-α及IL-1蛋白的表达.结果 在30 min、2 h、6 h及24 h各个时间点,D组大鼠血清ALT及AST水平、肝组织MDA含量及IL-1、TNF-α蛋白表达量明显低于C组,再灌注后2 h、6 h、24 h,D组大鼠肝组织SOD含量(411±70;384±53;379±46)和各时间点HIF-1α蛋白表达量(0.0413±0.0040;0.0684±0.0032;0.0583±0.0032;0.0491±0.0026)明显高于C组[SOD(341±21;323±25;303±25)和HIF-1α(0.0254±0.0024;0.0312±0.0022;0.0381±0.0022;0.0257±0.0015)](F>59.881;P<0.01).结论 去铁胺预处理对大鼠自体肝移植缺血再灌注损伤具有保护作用,可能与促进HIF-1α表达上调,减轻氧化损伤和降低炎性因子水平有关.

Deferoxamine pretreatment for hepatic ischemia reperfusion injury in liver auto-transplantation in rats

Objective To investigate the role of deferoxamine pretreatment for hepatic ischemia reperfusion injury in liver auto-transplantation in rats. Method Murine liver auto-transplantation model was established. Ninety six male Sprague-Dawley rats were randomly divided into three groups: 32 rats in deferoxamine pretreatment group (D), 32 rats in control group with aqua pro injection pretreatment(C) and 32 rats in sham-operation group (S). The animals were killed at 30 min, 2 h, 6 h, 24 h after operation respectively. ALT and AST level, superoxide dismutase (SOD) and malondialdehyde (MDA), liver histological change(HE), the protein expression of HIF-1α、TNF-α and IL-1 were measured. Results At 30 min, 2 h, 6 h, 24 h after operation, the levels of ALT,AST,MDA and the expression of IL-1 protein and TNF-α protein were higher in group C than group D significantly,while the expression of HIF-1α and SOD were higher in group D [SOD(411±70; 384±53; 379±46)、H1F-1α(0.0413±0.0040; 0.0684± 0.0032; 0.0583±0.0032; 0.0491±0.0026)] than group C significantly (P<0.01) [SOD(341±21; 323±25; 303±25)、HIF-1α (0.0254±0.0024; 0.0312±0.0022; 0.0381±0.0022; 0.0257± 0.0015)] (F>59.881;P<0.01). Conclusion The up-regulated expression of HIF-1α, decreased liver lipid peroxidation injury and TNF-α and IL-1 levels, may be involved in the mechanism hy which deferoxamine pretreatment protects liver from ischemia reperfusion injury in rats' liver auto-transplantation.