PEP-1介导血红素加氧酶-1对大鼠肝脏缺血／再灌注后SOD和MDA及Caspase-3表达的影响

Effects of PEP-1-mediated heme oxygenase-1 on SOD,MDA and Caspase-3 expressions rats with hepatic ischemia-reperfusion injury

目的：探讨大鼠肝缺血/再灌注（I/R）后PEP-1介导血红素加氧酶-1（HO-1）对肝脏超氧化物歧化酶（SOD）、丙二醛（MDA）及caspase-3的影响。方法制作肝I/R损伤动物模型，SD大鼠随机分为4组，即假手术组（S组），肝缺血再灌注组（I/R组）、HO-1组、PEP-1-HO-1组。I/R后12 h光镜及电镜下观察肝细胞病理学改变，检测血清ALT的水平、肝组织MDA的含量及SOD的活性，免疫组化染色检测肝组织caspase-3的表达。结果 PEP-1-HO-1组血清ALT、肝组织MDA变化幅度明显低于I/R组，肝组织SOD明显高于I/R组（P ＜0．05）。在电镜下观察，l/R组肝小叶结构紊乱，肝窦淤血，肝细胞水肿变性，肝细胞片状坏死。HO-1组和PEP-1-HO-1组上述改变明显减轻。在I/R组中，caspase-3较S组表达增强，而在HO-1组、PEP-1-HO1组中其表达较I/R组减弱。结论 PEP-1介导HO-1对肝I/R损伤有保护作用，其作用机制可能与减少氧自由基产生、减轻脂质过氧化反应及抑制caspase-3的表达有关。

Objective To investigate the effects of PEP-1-mediated heme oxygenase-1 （HO-1 ）on superoxide dismutase（SOD）and malondialdehyde（MDA）and Caspase-3 in rats with hepatic ischemia-reperfusion （I/R）injury.Methods Sprague-Dawley rats were used establish models of I/R injury and randomly divided into four group：the sham-operation group （S group ）,the hepatic I/R group,HO-1 group and PEP-1-HO-1 group.After 12h of reperfusion,liver tissues were harvested for the observation of pathological changes through light and electron microscope.The levels of serum ALT,hepatic MDA and SOD activity were tested.Expressions of hepatic Caspase-3 were tested with immunohistochemistry.Results Compared with the I/R group,the levels of serum ALT and hepatic MDA were significantly decreased with the increasing activity of SOD in the PEP-1-HO-1 group.Obvious I/R injury was observed under the electron microscope in the I/R group,including disor-dered structure of hepatic lobule,congestion in liver sinusoids,hydropic degeneration and patchy necrosis of hepatocyte.In the HO-1 group and PEP-1-HO-1 group,those hepatic tissue injuries were significantly improved. Comparing with the S group,the Caspase-3 expression in the I/R group increased and it＇s higher than those in the HO-1 group and PEP-1-HO-1 group.Conclusion PEP-1-mediated HO-1 protect liver from hepatic I/R in-jury.The mechanism of protection may be associated with the inhibition of oxygen radical,lipid peroxidation and Caspase-3 expression.