高血糖促进氧化应激加重大鼠心肌缺血/再灌注损伤

目的:研究高血糖是否可通过增加大鼠急性缺血/再灌注（I/R）心肌氧化应激而加重心肌损伤，并探讨其机制。方法: 将SD大鼠随机分为3组:假手术组(Sham)、生理盐水对照组(Vehicle)和高糖组(HG)。通过缺血30 min再灌注6 h，建立大鼠急性心肌I/R模型。通过静脉输注高浓度葡萄糖溶液，建立大鼠急性心肌I/R并发高血糖动物模型。术中监测血糖水平。再灌注结束后，检测血浆心肌酶谱水平，心肌梗死面积（IS）、心肌细胞凋亡指数（AI）和caspase 3的活性，检测心肌组织中氧化应激指标超氧阴离子、gp91phox、MDA、SOD，以及硫氧还蛋白结合蛋白（Txnip）的水平和硫氧还蛋白（Trx）的活性。结果: 与Vehicle组比较，HG组大鼠血糖水平显著升高，肌酸激酶（CK）、乳酸脱氢酶（LDH）的水平和IS增加，AI和caspase 3的活性升高(P<0.05)。HG组I/R心肌组织氧化应激程度显著升高，超氧阴离子、gp91phox和MDA水平增加(P<0.05)。同时，HG组I/R心肌组织的Txnip表达增加而Trx活性降低(P<0.05)。结论: 高血糖可增加大鼠I/R心肌中Txnip的表达，抑制Trx的活性促进氧化应激，这可能是其加重I/R心肌损伤的机制。

Hyperglycemia aggravates ischemia/reperfusion myocardial injury in rats through increased oxidative stress

AIM: To study the effects of hyperglycemia on oxidative stress and ischemia/reperfusion(I/R) myocardial injury in rats and the possible mechanisms.METHODS: Rats were subjected to 30 min of myocardial ischemia and 6 h of reperfusion and were randomly assigned to sham group,vehicle group(saline throughout ischemia and reperfusion period) or high glucose(HG) group(administration of 500 g/L glucose by i.v.infusion during ischemia and reperfusion period).Blood glucose levels were monitored throughout the experiments.Myocardial infarct size(IS) and serum myocardial enzymogram of rats were determined after the experiments.Apoptotic index(AI),caspase 3 activity,thioredoxin-interacting protein(Txnip) protein level and thioredoxin(Trx) activity were detected in I/R rats and were determined after the experiments.Apoptotic index,caspase 3 activity,superoxide,gp91phox,malondialdehyde(MDA),superoxide dismutase(SOD),and Txnip protein level of myocardium were also detected.RESULTS: Compared with vehicle group,HG group had significantly enlarged infarct size as well as increased creatine kinase,lactate dehydrogenase levels,AI and caspase 3 activity(P<0.05).At the same time,hyperglycemia increased oxidative stress as expressed by increased superoxide,gp91phox and MDA(P<0.05).Hyperglycemia increased Txnip protein expression in ischemia/reperfusion myocardium and decreased Trx activity.However,Trx protein was not affected.CONCLUSION: Hyperglycemia induces Txnip expression and decreases Trx activity in I/R myocardium.The resultant increased oxidative stress may be one of the mechanisms responsible for the exacerbated rat I/R myocardial injury induced by hyperglycemia.