L-精氨酸对肝缺血再灌注损伤的保护作用及其机制

Protective mechanism of L-Arginine against liver ischemic reperf usion injury in rats

目的 探讨L 精氨酸 (L Arg)对肝脏缺血再灌注 (I/R)损伤的保护及其机制。 方法雄性SD大鼠随机分为 :假手术组 (Sham ) :大鼠开腹游离肝十二指肠韧带 ,不阻断 ;对照组 (Con trol) :单纯入肝血流阻断 ;Arg组 :肝缺血前 5min ,从大鼠阴茎背静脉 (PDV )注射L Arg 2 0 0mg/kg体重 ;Arg +L组 :肝缺血前 10和 5min ,依次从大鼠PDV注射L 硝基精氨酸甲酯 (L NAME) 30mg/kg体重和L Arg 2 0 0mg/kg体重 ;fmk组 :肝缺血前 5min ,从大鼠PDV注射N 笨甲基氧化碳酰 缬氨酸 丙氨酸 天冬氨酸 氟化丙酮 (ZVAD fmk) 15mg/kg体重。各组入肝血流阻断时间为 40min ,比较各组的谷丙转氨酶 (ALT)、Caspase 3活性、肝细胞凋亡数和 7d生存率。 结果 肝缺血 40min再灌注 6h ,Arg组的 7d生存率显著高于对照组和Arg +L组 (P <0 .0 5 )。Arg组ALT、Cas pase 3活性和肝细胞凋亡数明显低于对照组和Arg +L组 (P <0 .0 1)。Arg组的Caspase 3活性和肝细胞凋亡数略高于fmk组和假手术组 (P >0 .0 5 )。结论 L Arg对肝脏I/R损伤有良好的保护作用 ,其保护机理可能是通过一氧化氮 (NO)作用于Caspase 3并使其失活 ,从而抑制肝细胞凋亡的发生而实现的。

Objective To investigate the protective e ffect of L-Arginine (L-Arg) against liver ischemic reperfusion (I/R) injury in rat model and clarify its possible mechanism.Methods Mal e SD rats were randomized into the following groups:Sham group:hepatoduodenal li gment was mobilized,but not clamped;Control group:hepatic ischemia only;Arg grou p:5 min before hepatic ischemia,L-Arg (200 mg/kg) was injected via the dorsal p enis vein;Arg+L group:10 min and 5 min before hepatic ischemia,L-NAME (30 mg/kg ) and L-Arg (200 mg/kg) were injected via the dorsal penis vein,respectively;Fm k group:5 min before hepatic ischemia,ZVAD-fmk (15 mg/kg) was injected via the dorsal penis vein.The liver was subjected to ischemia for 40 min by the Pringle' s maneuver,and reperfusion was initiated by removing clamp.The 7-day survival r ate,alanine ALT,Caspase-3 activity and apoptotic hepatocytes were compared amon g these groups.Results After 40 min of ischemia and 6 h o f reperfusion,the 7-day survival rate in Arg group was significantly higher tha n in control and Arg+L groups(P<0.05).The ALT level,Caspase-3 activity and apoptotic hepatocytes in the Arg group were decreased significantly as compared with those in the control and Arg+L groups(P<0.01).The Caspase-3 activity and apoptotic hepatocytes in the Arg group were slightly higher than those in t he Sham and fmk groups,but there was no statistical significance.Conc lusion The possible protective mechanism by which L-Arg could ameli orate liver I/R injury might be contributed to the inhibition of hepatocyte apop tosis through inactivating Caspase-3 activity by nitric oxide.