吡格列酮对糖尿病大鼠心肌缺血再灌注损伤的影响

Effects of pioglitazone on myocardial ischemia-reperfusion injury in diabetic rats

目的观察糖尿病大鼠心肌缺血再灌注(MIR)时细胞间黏附分子-1(ICAM-1)和自由基代谢的变化及吡格列酮对其的影响,探讨糖尿病大鼠MIR损伤的机制。方法制作糖尿病大鼠模型,4周后作MIR模型。糖尿病大鼠30只分为假手术对照(sham)组,MIR组和吡格列酮组。免疫组织化学法检测心肌ICAM-1蛋白表达。检测血清、心肌组织超氧化物酶(SOD)、丙二醛(MDA)、谷胱甘肽-过氧化物酶(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(P<0.05),血清SOD明显降低(P<0.01),心肌SOD和血清、心肌GSH-PX明显降低(P<0.05),血清、心肌MDA明显升高(P<0.05),心肌ICAM-1蛋白表达明显升高(P<0.01)。用吡格列酮4周后线粒体Na+,K+-ATP酶、Mg2+-ATP酶、Ca2+-ATP酶活性高于MIR组(P<0.05),血清、心肌SOD和GSH-PX水平高于MIR组(P<0.05),心肌MDA低于MIR组(P<0.01),心肌ICAM-1蛋白表达低于MIR组(P<0.05)。结论吡格列酮可减轻糖尿病心肌缺血再灌注损伤。

Objective To observe the effects of pioglitazone on the changes of the intercellular adhesion molecule-1 （ICAM-1） and free radicals in ischemia-reperfused myocardium（MIR） of diabetic rats, and investigate the reasons of myocardial ischemia-reperfusion injury in diabetic rats. Methods The diabetic rat model was established by streptozotocin injection to the abdominal cavity of Spraque- Dawlay rats. Four weeks later, the myocardial ischemic-reperfused models were established in anesthetic SD rats. Thirty SD rats were divided into three groups with 10 rats each （sham group,MIR group and pioglitazone group ）. The ICAM-1 protein expressions were evaluated by immunocytochemistry. The contents of malondialdehyde（MDA） in serum and myocardial tissues were detected. The activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-PX） in serum and myocardial tissues were measured. The activities of Mg^2＋-ATPase, Ca^2＋-ATPase and Na^＋ ,K^＋-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 （P〈0. 05）, the contents of MDA in serum and myocardium were increased significantly （P〈 0. 05） , the activities of GSH-PX in serum and myocardium were decreased significantly （P〈0. 05）, the activities of SOD in serum and myocardium （P〈0. 01 and P〈0.05, respectively） were decreased significantly, the expression levels of ICAM-1 protein in myocardium were increased significantly in MIR group （P〈0. 01）. Compared with MIR group, the activities of Na^＋, K^＋-ATPase, Mg^2＋-ATPase, Ca^2＋-ATPase in myocardial mitochondria were increased significantly （P〈0. 05）, the contents of MDA in myocardium were decreased significantly （P〈 0. 01）, the activities of SOD and GSH-PX in serum and myocardium were increased significantly （P〈 0. 05）, the expression levels of ICAM-1 protein in myocardium were decreased significantly in pioglitazone group （P〈 0.05）. Conclusions Pioglitazone could relieve myocardial ischemia- reperfusion injury induced by MIR in diabetic rats.