左旋精氨酸对肝移植大鼠热缺血损伤的防护

Protection against Warm Ischemia Injury by L-Arginine

目的 探讨不同热缺血时间对肝移植大鼠血清TNFα的影响及左旋精氨酸对热缺血损伤的防护作用。方法 Wistar大鼠 10 4只 ,随机取 8只为正常对照组 (N组 ) ,另 96只随机分为 6组。C1 、C2 、C3 组为实验对照组 ,E1 、E2 、E3 组为实验组。C1 与E1 、C2 与E2 、C3 与E3 分别行热缺血时间 0、3 0、45min供肝肝移植 ;N组取血及肝组织备检。各实验对照组则用等量生理盐水作对照。移植完成后 ,于PV复流后 1、3、2 4h检测血清肿瘤坏死因子α(TNFα)、丙氨酸氨基转移酶 (ALT)、天冬氨酸氨基转移酶 (AST)水平 ,观察肝组织超微结构。结果 与N组相比 ,各实验组与实验对照组大鼠PV复流后 1h ,血清TNFα水平明显升高 (P <0 .0 5) ;与对应的实验对照组相比 ,各实验组在PV复流后 1、3h血清TNFα水平明显降低 (P <0 .0 5) ,实验对照组之间相比 ,C3 、C2 组大鼠血清TNFα水平明显高于C1 组 (P <0 .0 5) ,C3 组明显高于C2 组 (P <0 .0 5)。电镜下 ,各实验组与实验对照组肝组织病理损害较N组为重 ,各实验组病理损害较对应实验对照组明显减轻。结论 TNFα可能是参与供肝热缺血再灌注损伤的主要细胞因子之一 ;左旋精氨酸预处理可能通过减少TNFα释放 ,从而减轻热缺血对移植肝的损伤。

Objective To investigate the influence of different warm ischemia time on serum TNFα of recipients rats and protection against warm ischemia injury by L-Arginine. Methods 104 wistar rats were randomly divided into 6 groups: normal control group (Group N,n=8), control group C 1, C 2, C 3, experimental group E 1, E 2, E 3. For group C 1 and E 1, group C 2 and E 2, group C 3 and E 3, the warm ischemia time was 0, 30, and 45 min, respectively , Liver grafts were flushed with and preserved in Euro-collins solution.Donors and recipients of each experimental control group were treated with normal saline. Then transplantation was performed. At 1, 3, and 24h after portal vein reperfusion, blood samples were obtained todetermine the levels of TNFα , ALT, AST for electronscopy observation. Results At 1h after portal vein reperfusion, the levels of TNFα in all experiment group and all control group were significantly higher than that in normal control group after PV reperfusion(P<0.05); at 1h, 3h, the levels of TNFα in experiment group were significantly lower than that in corresponding control group(P<0.05),The levels of TNFα in group C 3 and C 2 were significantly higher than that in group C 1 (P<0.05), and the levels of TNFα in group C 3 were significantly higher than that in group C 2 (P<0.05). Pathological changes in all experiment group were significantly milder than that in corresponding experimental control groups. Conclusion TNFα play an important role in the development of warm ischemia reperfusion injury of liver graft. L-Arg could attenuate liver graft injury by decreasing production of TNFα.