目的 观察糖原合成激酶3β（glycogen synthase kinase-3β， GSK-3β）在二氮嗪（diazoxide， DZ）后处理糖尿病大鼠心肌缺血/再灌注损伤（ischemia/reperfusion injury， I/RI）中的作用及机制。 方法 单次腹腔注射链脲佐菌素（streptozotocin， STZ）制备糖尿病大鼠模型，取造模成功的大鼠48只，复制在体心肌缺血/再灌注（ischemia/reperfusion， I/R）模型，按随机数字表法分为4组（每组12只）：假手术组（Sham组）、I/R组（I组）、DZ组（D组）、SB216763+DZ组（S组）。连续监测血流动力学指标，比色法测血浆乳酸脱氢酶（lactate dehydrogenase， LDH）活性，2，3，5-氯化三苯基四氮唑（triphenyl tetrazolium chloride， TTC）染色分析心肌梗死面积，Western blot测磷酸化GSK-3β（phosphorylated GSK-3β， pGSK-3β）的表达。 结果 与I组及D组比较，S组心功能明显改善（P<0.05），血浆LDH［S组、I组、D组为（5 335±502）、（7 943±831）、（7 176±521） U/L，P<0.05］活性及心肌梗死面积［S组、I组、D组为（21.0±1.6）%、（30.8±3.8）%、（31.3±2.9）%，P<0.05］均显著降低，pGSK-3β表达增加（P<0.05）；I组与D组比较上述指标差异无统计学意义（P>0.05）。 结论 DZ后处理对糖尿病大鼠心肌I/RI无保护作用，GSK-3β抑制剂干预后DZ后处理对糖尿病大鼠心肌I/RI的保护作用恢复。
Ｏｂｊｅｃｔｉｖｅ To observe the role and mechanism of glycogen synthase kinase-3β（GSK-3β） in myocardial ischemia/reperfusion injury（I/RI） by diazoxide（DZ） postconditioning in diabetic rats. Methods The diabetic rat model was established by single intraperitoneal injection of streptozotocin. After the model was duplicated successfully， in vivo myocardial ischemia/reperfusion（I/R） model was developed in 48 rats. Then the rats were randomly divided into 4 groups（n=12）： sham operation group（group Sham）， I/R group（group I ）， DZ group（group D）， SB216763 and DZ group（group S）. Hemodynamic parameters were monitored continuously. The plasma cardiac enzymes lactate dehydrogenase（LDH） and myocardial infarct size were measured by colorimetric measurement and 2，3，5-triphenyltetrazolium chloride（TTC） staining， respectively. The protein expression of phosphorylated GSK-3β（pGSK-3β） in the heart was detected by Western blot. Results Compared with group I and group D， cardiac function was improved in group S（P<0.05）. The levels of plasma LDH ［group S vs group I vs group D： （5 335±502） U/L vs （7 943±831） U/L and （7 176±521） U/L， P<0.05］ and myocardial infarct size［group S vs group I vs group D： （21.0±1.6）% vs （30.8±3.8）% and （31.3±2.9）%， P<0.05］ significantly decreased. The expression of pGSK-3β was increased（P<0.05）. There was no significant difference between group I and D（P>0.05）. Conclusions DZ postconditioning can't protect diabetic rat heart against I/RI， but can exert the protective function after interfered with GSK-3β inhibitor.
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