腺苷2A受体激活减轻小体积肝移植中的氧化应激反应

Activation of Adenosine 2A Receptor Attenuating Oxidative Stress on Small-for-Size Liver Transplantation

目的通过大鼠小体积肝移植模型研究腺苷2A受体(adenosine2Areceptor,A2AR)激动对氧化应激反应的影响。方法将18只Lewis大鼠建立的小体积肝移植受体模型随机均分为对照组、激动组及激动+拮抗组,并于再灌注后6h分别检测血浆丙氨酸氨基转移酶(aspartate aminotransferase,AST)、酶类抗氧化物〔超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)、谷胱苷肽过氧化物酶(glutathione peroxidase,GSH-Px)〕及非酶类抗氧化物〔抗坏血酸(ascorbic acid,AA)、谷胱苷肽(glutathione,GSH)、α-生育酚(α-tocopherol,TOC)〕和丙二醛(malondialdehyde,MDA)的水平。结果与对照组及激动+拮抗组比较,激动组SOD和GSH-Px活性均明显增加(P<0.05),而CAT活性无明显变化(P>0.05);MDA含量及AST水平均显著下降(P<0.05);AA、GSH、TOC水平均显著提高(P<0.05)。结论A2AR激活明显增加了肝脏酶类抗氧化物活性,上调了非酶类抗氧化物的表达,抑制了毒性抗氧化产物MDA含量及AST的水平上升,提示A2AR激活抑制了脂质氧化损伤,增强了抗氧化能力,从而减少了在小体积肝移植中的缺血再灌注损伤。

Objective To investigate the effects of adenosine 2A receptor（A2AR）activation on oxidative stress in small-for-size liver transplantation.Methods A rat orthotopic liver transplantation model was performed using 40% graft,18 recipients were given intravenously saline（control group）,CGS21680（A2AR agonist,CGS21680 group）or ZM241385（A2AR antagonist,CGS21680＋ZM241385 group）randomly.Aspartate aminotransferase（AST）,enzymatic antioxidants 〔superoxide dismutase（SOD）;catalase（CAT）;glutathione peroxidase（GSH-Px）〕,non-enzymatic antioxidants 〔ascorbic acid（AA）;glutathione（GSH）;α-tocopherol（TOC）〕 and lipid oxidant metabolites malondialdehyde（MDA）were measured and analyzed at 6 h after reperfusion.Results Compared with the control group and CGS21680＋ZM241385 group,A2AR activation increased the activities of SOD and GSH-Px（P〈0.05）,reduced the productions of AST and MDA（P〈0.05）,increased the levels of AA,GSH and TOC（P〈0.05）in CGS21680 group.But there was no significant change in CAT activity（P〉0.05）among 3 groups.Conclusions A2AR activation improves the antioxidant enzyme activities,promotes the production of antioxidants,and slowes down the increase in MDA level,depresses of the increase in AST activity.A2AR activation suppresses oxidative damage and increases the antioxidant capacity which in turn minimizes their harmful effects of ischemia-reperfusion in small-for-size liver transplantation.