缺血和药物预处理对大鼠肝缺血再灌注损伤的保护作用

Ischemia preconditioning and medicine preconditioning protects against ischemia-reperfusion injury of rats liver

目的探讨缺血预处理(IPC)和潘生丁预处理(DPC)对大鼠肝缺血再灌注损伤(IR)的保护作用及发生机制。方法建立大鼠肝脏肝缺血再灌注模型,对肝分别作缺血及药物预处理。观察各组处理后肝组织中腺苷含量,1h后取门静脉血测定血清谷草转氨酶(ALT)、乳酸脱氢酶(LDH)、肿瘤坏死因子-α(TNF-α)及内皮素1(ET-1),同时取肝组织行病理组织学检查及肝组织髓过氧化物酶(MPO)含量测定。结果IPC、DPC后肝组织中腺苷水平升高,与对照组相比差异显著(P<0.01)。缺血再灌注1h后ALT、LDH及TNF-α、ET-1均明显高于正常对照组,潘生丁组及缺血预处理组则明显低于缺血再灌注组。潘生丁组及缺血预处理组的肝脏病理组织学改变明显轻于缺血再灌注组,并接近正常对照组。结论潘生丁预处理及缺血预处理对肝缺血再灌注具有保护作用,均与腺苷有关,潘生丁可模拟IPC的保护作用。

[Objective] To investigate the protective mechanism of dipyridamole preconditioning and ischemia preconditioning against hepatic ischemia reperfusion injury. [Methodsl Using ischemia-reperfusion rat model in normal temperature, ischemia preconditioning and medicine preconditioning before ischemia. The content of adenosine phosphates in liver was examined. An hour later blood was taken from portal vein to examine the enzyme levels, including ALT, LDH and TNF-α, ET-1. The alteration of pathological morphology of the ischemia lobe was observed. The content of myeloperoxldase （MPO） in liver was examined. [Results] A significant increase in adenosine was found immediately after the hepatic IPC, DPC as compared with the control group （P 〈0.01）. The two enzemes, TNF-α, ET-1 levels of ischemia-reperfusion group were significantly higher than those of the control group （P 〈 0.01）. The indices of the dipyridamole group were much lower than those of the ischemia-reperfusion group （P 〈 0.01）, but little higher than those of the control group （P 〉0.05）. The control group had obvious alteration in pathological morphology, but only slight alteration in IPC, DPC group, compared with the control group. [Conclusion] Dipyridamole preconditioning and ischemla preconditioning protect against ischemia-reperfusion injury of the livet. Adenosine may play an critical role for the protection. Dipyridamole preconditioning might imitate the effect of IPC.