摘要
目的研究吡咯列酮对糖尿病大鼠心脏缺血再灌注的保护作用及机制。方法链脲佐菌素腹腔注射建立糖尿病大鼠模型,将糖尿病大鼠45只随机分为5组:假手术组,缺血再灌注组,吡格列酮5 mg/kg组,吡格列酮10 mg/kg组和吡格列酮20 mg/kg组,每组9只,利用体内结扎左前降支的方法建立缺血再灌注损伤模型,取大鼠心肌组织,检测细胞凋亡、丙二醛(MDA)、超氧化物歧化酶(SOD)、Bax、Bcl-2、Cytochrome c和Smac/DIABLO和半胱氨酸天冬酶9、3(Caspase 9、3)的变化。结果与缺血再灌注组相比,吡格列酮5、10和20 mg/kg可呈剂量依赖性减少MDA含量、Bax蛋白表达、Caspase 9、3酶活性,增加SOD酶活性和Bc-l2蛋白表达,抑制细胞凋亡。结论吡格列酮预处理可降低糖尿病大鼠心肌缺血再灌注后细胞的氧化损伤水平,下调线粒体凋亡蛋白表达,减少心肌细胞凋亡数以起到心肌保护作用。
Objective To study on mechanism of protecting the myocardium from ischemia-reperfusion injury by pioglitazone in diabetic rat. Methods The diabetic rat models were established by intraperitoneal injection of streptozotocin, forty-five diabetic rats were randomly divided into five groups： sham operation group, ischemia-reperfusion group, pioglitazone 5 mg/kg, treated group, pioglitazone 10 mg/kg treated group and pioglitazone 20 mg/kg treated group. Left anterior descending coronary artery was ligated for 30 min and reperfused for 120 min to establish the model of ischemia-reperfusion in vivo. TUNEL, Maleic dialdehyde （MDA）, superoxide dimutese （SOD）, Bax, Bcl-2, Cytochrome c and Smac/DIABLO proteins and caspase 9, 3 were detected in rat myocardial tissue. Results Comparing with the ischemia-reperfusion group, the expressions of Bax and Caspase 9, 3 were depressed, levels of cytosolic Cytochrome c and Smac/ DIABOL proteins and MDA contents were decreased, while the expression of Bcl-2 and SOD activities were increased by pioglitazone in a dose-dependent manner. Conclusion Pioglitazone could protect the diabetic rat heart from ischemia-reperfusion injury evidenced by reduce oxidative damage, down-regulated mitochondrial apoptotic protein expression and decrease cell apoptosis.
出处
《毒理学杂志》
CAS
CSCD
北大核心
2014年第1期30-34,共5页
Journal of Toxicology
