预处理对大鼠心肌缺血再灌注损伤的影响

Effects of preconditioning on myocardial ischemic reperfusion injury of rats

目的观察大鼠心肌缺血再灌注(MIR)时ICAM-1和自由基代谢的变化及吡格列酮预处理、肾脏缺血预处理(RIP)对其的影响,探讨大鼠MIR损伤的机制。方法大鼠40只,分为假手术对照(sham)组,MIR组,RIP组和吡格列酮预处理组。免疫组织化学法检测心肌ICAM-1蛋白表达。检测血清、心肌组织SOD、MDA和GSH-PX及心肌线粒体Na+,K+-ATP酶、Mg2+-ATP酶、Ca2+-ATP酶活性。结果与sham组相比,MIR组心肌线粒体Na+,K+-ATP酶、Mg2+-ATP酶、Ca2+-ATP酶活性明显下降;RIP和吡格列酮预处理后心肌线粒体Na+,K+-ATP酶、Mg2+-ATP酶活性均明显高于MIR组。与sham组相比,MIR组心肌MDA明显升高,血清、心肌SOD和GSH-PX明显降低,RIP后血清、心肌MDA低于MIR组,血清、心肌SOD水平高于MIR组,用吡格列酮4周后血清、心肌MDA低于MIR组,血清、心肌SOD和GSH-PX水平高于MIR组。与sham组相比,MIR组心肌ICAM-1蛋白质表达明显升高;RIP和吡格列酮预处理后心肌ICAM-1蛋白质表达均低于MIR组。结论MIR时有大量ICAM-1蛋白表达,与心肌损伤关系密切。肾脏缺血和药物两种预处理方式均可通过减少ICAM-1蛋白表达水平,起心肌保护作用。RIP可能通过增加某些自由基的生成来诱导保护性蛋白的合成。药物预处理能加速自由基的清除,增强机体的抗氧化能力,从而保护心肌组织免受氧化损伤。

[Objective] The aim of this study was to observe the effects of Piogtazone and Renal ischemic preconditioning （RIP） on the changes of the intercellular adhesion molecule-1 （ICAM-1） and free radicals in ischemic reperfusion myocardium, and to investigate the mechanism of myocardial ischemic repeffusion injure. [Methods] Forty SD rats were divided into four groups with each group having 10 rats （sham group, MIR group, RIP group and piogtazone group）. The ICAM-1 protein expressions were evaluated by immunohistochemical method. The quantities of malonialdehyde （MDA） in serum and myocardial tissues were tested. The activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-PX） in serum and myocardial tissues were measured. The activities of Na^＋, K^＋- ATPase, Mg^2＋-ATPase, Ca^2＋-ATPase in myocardial mitochondria were measured. [Results] Compared with sham group, the activities of Na^＋, K^＋-ATPase, Mg^2＋-ATPase, Ca^2＋-ATPase in myocardial mitochondria were decreased significantly in MIR group. The activities of Na^＋, K^＋-ATPase, Mg^2＋-ATPase, Ca^2＋-ATPase in myocardial mitochondria were increased significantly in RIP and piogtazone group compared with MIR group. Compared with sham group, the quantities of in MDA in serum and myocardium were increased significantly, the levels of SOD and GSH-PX in serum and myocardium were decreased significantly in MIR group. Compared with MIR group, the levels of MDA in serum and myocardium were decreased significantly, the activities of SOD in serum and myocardium were increased significantly in piogtazone and RIP group. Compared with MIR group, the activities of GSH-PX in serum and myocardium were increased significantly in piogtazone group. Compared with sham group,the levels of ICAM-1 in myocardium were increased significantly in MIR group. The levels of ICAM-1 in myocardium were decreased significandy in RIP and piogtazone group compared with MIR group. [Conclusions] The findings indicated that piogtazone and RIP could relieve myocardial ischemic reperfusion injure induced by MIR, and this action was mediated by the reduction of the expression of ICAM-1 protein. RIP induces protective protein by increasing the levels of free radicals. Piogtazone plays key roles in protective effects on myocardial ischemic reperfusion injury probably by scavenging free radicals, decreasing the levels of MDA in serum and myocardium and increasing the level of SOD and GSH-PX in serum and myocardium, the level of Na^＋, K^＋-ATPase, Mg^2＋-ATPase, Ca^2＋-ATPase in myocardial mitochondria.