Najafi Moslem, Farajnia Safar, Mohammadi Mustafa, Badalzadeh Reza, Ahmadi Asl Naser, Baradaran Behzad, Amani Mohammad
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
J Diabetes Metab Disord. 2014 Nov 18;13(1):106. doi: 10.1186/s40200-014-0106-1. eCollection 2014.
Cardiovascular risk factors, including diabetes mellitus may attenuate the cardioprotection by postconditioning. This study aimed to investigate the cardioprotective effect of ischemic-postconditioning (IPostC) against ischemia/reperfusion injury in normal and chronically type-1 diabetic rats and the effect of mitochondrial permeability transition pore (mPTP) inhibition in this field.
Diabetes was induced by a single intra-peritoneal injection of streptozotocin (50 mg/kg) in Wistar male rats (250-300 g). After 8 weeks, the hearts of control and diabetic animals were isolated and mounted on a constant-pressure Langendorff apparatus. All hearts were subjected to 30 min regional ischemia followed by 45 min reperfusion (by occluding and re-opening of LAD coronary artery, respectively). At the end of ischemia, the hearts received IPostC, cyclosporine-A, or both or none of them. Myocardial creatine-kinase (CK) release as an index of tissue injury was measured spectrophotometery in coronary effluent in reperfusion phase. Infarct size was identified by triphenyltetrazolium chloride staining. Heart rate, left ventricular end-diastolic pressure (LVEDP), LV systolic pressure (LVSP), rate-pressure product (RPP) and coronary flow were recorded throughout the experiment.
IPostC, applied at the onset of reperfusion, failed to improve myocardial LVEDP and RPP, or reduce tissue damage indicated by infarct size and CK release in diabetic hearts, while it significantly recovered these parameters toward the pre-ischemic values in control hearts (P < 0.05). In contrast, with simultaneous inhibition of mPTP using cyclosporine-A, the cardioprotective effects of IPostC on myocardial hemodynamics, infarct size and CK release were significantly restored in diabetic hearts (P < 0.05).
The loss of cardioprotection by IPostC in diabetic state can be overcome by increasing the potency of protective IPostC through its co-application with mPTP inhibition.
包括糖尿病在内的心血管危险因素可能会减弱缺血后适应的心脏保护作用。本研究旨在探讨缺血后适应（IPostC）对正常和慢性1型糖尿病大鼠缺血/再灌注损伤的心脏保护作用，以及线粒体通透性转换孔（mPTP）抑制在此过程中的作用。
通过向雄性Wistar大鼠（250 - 300 g）腹腔注射一次链脲佐菌素（50 mg/kg）诱导糖尿病。8周后，分离对照和糖尿病动物的心脏，并安装在恒压Langendorff装置上。所有心脏均经历30分钟的局部缺血，随后进行45分钟的再灌注（分别通过阻断和重新开放左冠状动脉前降支）。在缺血结束时，心脏接受IPostC、环孢素A，或两者都接受或两者都不接受。在再灌注期，通过分光光度法测量冠状动脉流出液中心肌肌酸激酶（CK）的释放，作为组织损伤的指标。通过氯化三苯基四氮唑染色确定梗死面积。在整个实验过程中记录心率、左心室舒张末期压力（LVEDP）、左心室收缩压（LVSP）、速率压力乘积（RPP）和冠状动脉流量。
在再灌注开始时应用IPostC，未能改善糖尿病心脏的心肌LVEDP和RPP，也未能减少梗死面积和CK释放所表明的组织损伤，而在对照心脏中，它能使这些参数显著恢复到缺血前的值（P < 0.05）。相反，同时使用环孢素A抑制mPTP，IPostC对糖尿病心脏的心肌血流动力学、梗死面积和CK释放的心脏保护作用得到显著恢复（P < 0.
