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

摘要

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.d 4,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.