无创性肢体缺血预适应对不同病程糖尿病大鼠缺血/再灌注心肌的保护作用

Cardioprotection of noninvasive limb ischemic preconditioning against ischemia-reperfusion injury in myocardium with different duration of diabetes mellitus in rats

目的研究无创性肢体缺血预适应(noninvasive limb ischemic preconditioning,NLIP)对1周和4周病程糖尿病(DM)大鼠心肌缺血/再灌注损伤的保护作用。方法大鼠经尾静脉1次性注射链脲佐菌素(STZ)制备成1周和4周病程的DM模型后,被随机分为假手术(Sham)、缺血/再灌注(I/R)、心脏缺血预适应(CIP)和无创肢体缺血预适应(NLIP)4组。NLIP组连续3 d经历左后肢缺血预适应。d4,I/R、CIP和NLIP组动物经历心肌缺血/再灌注损伤,CIP组于缺血前行心肌缺血预适应,Sham组经冠状动脉左前降支(LAD)下穿线不结扎。连续监测血压和心电图变化,检测心肌梗死范围,测定血清CK-MB、LDH活性。结果成模动物表现出血糖明显升高,体重下降。NLIP可明显降低1周和4周病程DM动物室性早搏(VPC)和室性心动过速(VT)的发生率,推迟1周病程DM模型缺血期间VPC的出现时间并缩短其持续时间,与CIP作用程度相当,同时可缩短4周病程DM动物VPC持续时间。与1周病程比较,4周病程I/R组动物心肌梗死面积明显增加;NLIP与CIP均可使两病程动物心肌梗死面积明显缩小。与I/R组比较,两病程动物NLIP与CIP组CK-MB、LDH活性明显降低。结论 NLIP对1周和4周病程DM动物均具有延迟相心脏保护作用。

Aim To investigate the effects of noninvasive limb ischemic preconditioning（NLIP） on myocardium after ischemia-reperfusion injury in streptozotocin（STZ） induced diabetic rats with different duration（one-week and four-week）.Methods Rats received a single injection of STZ through the tail vein and acute diabetes mellitus of one-week and four-week duration was induced.The diabetic rats were divided randomly into sham,ischemia-reperfusion（I/R）,cardiac ischemic preconditioning（CIP） and NLIP groups.Diabetic rats in NLIP group were subjected to NLIP for 3 days.On the next day,diabetic rats in I/R,CIP,NLIP groups were subjected to myocardial ischemia-reperfusion injury.Diabetic rats in CIP group were preconditioned before ischemia.Diabetic rats in sham group were threaded a silk suture under the left coronary artery anterior descending（LAD） and laid up.Blood pressure and ECG were monitored.Myocardial infarct size was examined.Activities of CK-MB and LDH were detected.Results All the diabetic rats exhibited increased level of blood glucose and reduction of body weight.NLIP significantly decreased the incidence of ventricular premature contraction（VPC） and ventricular tachycardia（VT） during ischemia in diabetic rats with one-week and four-week duration,delayed onset and shortened duration of VPC in diabetic rats with one-week duration,which reached to the extent of that by CIP,and shortened duration of VPC in diabetic rats with four-week duration.Compared with diabetic rats with one-week duration,myocardial infarct size of I/R group was significantly increased in diabetic rats with four-week duration;NLIP and CIP obviously reduced myocardial infarct size in diabetic rats with one-week and four-week duration.Compared with I/R group,activities of CK-MB and LDH were decreased in NLIP and CIP groups of diabetic rats with one-week and four-week duration.Conclusion NLIP has a similar delayed cardioprotection in diabetic rats with one-week and four-week duration.