【摘要】 目的　探讨缺血预处理 (IPC)保护作用的发生机制。方法　建立大鼠部分肝脏热缺血再灌注模型。IPC采用肝脏缺血 10min ,再灌注 10min。结果　IPC后肝组织中腺苷和NO水平明显升高 ,与对照组相比差异显著 (P <0 0 1) ,但IPC前应用腺苷A2 受体拮抗剂后NO的升高被抑制 (P<0 0 1)。缺血再灌注 (I/R) 2h后血清中TNF α、AST、ALT、LDH及W/D水平和假手术组相比明显增加 ,而IL 10含量降低 (P <0 0 1) ;IPC、I/R前加入腺苷、IPC前应用腺苷A1受体拮抗剂显著地降低TNF α释放和AST、ALT、LDH及W /D水平 ,提高IL 10含量 ,与I/R组相比差异显著 (P <0 0 1) ;但IPC前应用腺苷A2 受体拮抗剂 (IPC +A2 antag)和NO合成酶抑制剂NAME并没有能像IPC组那样有效降低TNF α、AST、ALT、LDH及W /D的水平 ,提高IL 10的含量 (P <0 0 1) ;而IPC前给IPC+A2 antag组提供NO前体精氨酸又获得和IPC组同样的结果 (P >0 0 5 )。结论　IPC引起细胞外腺苷水平升高 ,腺苷A2 受体活化 ,介导了NO合成增加 ,最终通过抑制效应器TNF α的释放、增加IL 10的合成来实现对缺血组织的保护作用。更多还原

【Abstract】 ObjectiveTo investigate the molecular mechanism of classic ischemic preconditioning （IPC） to induce ischemic tolerance. MethodsAfter the models of sham-operation and partial hepatic ischemia were established in rats, IPC was performed with a 10-min ischemia followed by a 10-min reperfusion. ResultsA significant increase in adenosine and NO production was found immediately after the hepatic IPC as compared with the control group （P<0.01）. This increase in NO content was markedly prevented by the administration of adenosine A₂ receptor antagonist to the IPC group （P<0.01）. An obvious decrease in release of TNF-a and an increase in production of IL-10 were found in IPC group at the 2nd h after reperfusion （P<0.01）. The levels of AST, ALT, LDH and W/D were significantly lower in IPC group than in I/R group （P<0.01）. The values of these parameters were remarkably decreased by administration of adenosine in the I/R group （P<0.01）. Pretreatment with adenosine A₁ receptor antagonist resulted in increase of TNF-a, AST, ALT, LDH and W/D levels but decrease of IL-10. However, pretreatment with adenosine A₂ receptor antagonist and NAME abolished the protective effects of IPC. The administration of NO precursor to the IPC+A₂ antagonist group prevented the injurious effect of A₂ receptor antagonist on hepatic IPC, leading to the same results as those observed in the IPC group. ConclusionsAn elevated adenosine extracellular concentration induces the activation of adenosine A₂ receptor, which, in turn, by induction of NO synthesis and subsequent prevention of TNF-a liberation and promotion of IL-10 production, confers cytoprotection to ischemic tissue.更多还原