糖尿病对缺血预适应大鼠心肌缺血再灌注的影响及其机制研究

Influence of diabetes on myocardial ischemic preconditioning and its mechanism

目的探讨糖尿病对缺血预适应(IPC)大鼠心肌缺血再灌注(I/R)的影响及其可能机制。方法取糖尿病SD大鼠及非糖尿病SD大鼠各30只,建立冠状动脉阻断的在体心肌I/R模型,各分为3组(n=10):假手术(Sham)组开胸后穿线做套环,但不收紧结扎线,持续155min,全程旷置作为基础水平对照;I/R组手术穿线平衡35min后,持续收紧结扎冠状动脉主干造成缺血30min,放松后行再灌注90min;IPC组手术穿线平衡35min后,缺血5min,再灌注5min,反复3次,而后重复I/R组操作。测定各组缺血前及实验结束后的血清肌酸激酶(CK)、乳酸脱氢酶(LDH)水平,心肌组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性,心肌梗死范围以及心肌葡萄糖摄取率。结果非糖尿病大鼠中,I/R组和IPC组CK、LDH活性及MDA含量显著高于Sham组(P<0.01或P<0.05),且I/R组显著高于IPC组(P<0.05或P<0.01);I/R组及IPC组SOD活性显著低于Sham组(P<0.01),且I/R组显著低于IPC组(P<0.05);IPC组心肌梗死面积显著低于I/R组(P<0.05),而心肌葡萄糖摄取率显著高于I/R组(P<0.05)。在糖尿病大鼠中,IPC组与I/R组的上述指标比较均无统计学差异(P>0.05)。结论糖尿病可抑制IPC对在体大鼠缺血再灌注心肌的保护作用,其机制可能与心肌胰岛素抵抗有关。

Objective To explore the influence of diabetes on myocardial ischemia reperfusion（I/R） in ischemic preconditioning（IPC） rats and its underlying mechanism.Methods Thirty diabetic and thirty non-diabetic SD rats were chosen and respectively divided into three groups（n=10） randomly.Sham operation group（Sham group）： after thoracotomy,a thread was passed under the coronary but without ligation,and 155 min later the experiment was ended.Ischemia reperfusion group（I/R group）： after thoracotomy,a thread was passed under coronary artery,wait for 35 min,and then the ligature was lightened for 30 min to produce ischemia and then followed by 90 min of reperfusion.Ischemic preconditioning group（IPC group）： after thoracotomy,a collar was made by threading method,balanced for 35 min,and then the rats were subjected to 5 min of ischemia and 5 min of reperfusion for 3 cycles,followed by 30 min of ischemia and 90 min of reperfusion.The contents of serum creatine kinase（CK）,lactate dehydrogenase（LDH）,myocardial malonyldialdehyde（MDA）,and superoxide dismutase（SOD） were determined,and the extent of myocardial infarction and myocardial glucose uptake rate were also assessed before ischemia and after the end of the experiment in all groups.Results In non-diabetic rats,the CK,LDH,and MDA contents were significantly higher in I/R and IPC group than those in Sham group（P〈0.05 or 0.01）,and were significantly higher in I/R group than in IPC group（P〈0.05 or 0.01）,while the SOD was significantly lower in I/R and IPC group than in Sham group（P〈0.01）,and was significantly lower in I/R group than in IPC group（P〈0.01）.The area of myocardial infarction was lower,while the myocardial glucose uptake rate was higher in IPC group than in I/R group（P〈0.05）.In diabetic rats,no obvious difference of the above index was found between IPC and I/R group（P〉0.05）.Conclusion Diabetes may counteract the protective effect of ischemic preconditioning on myocardial ischemia reperfusion injury in rats;the mechanism may be related to the insulin resistance of myocardium.