维格列汀预处理的糖尿病大鼠再灌注损伤后缺血后处理对心肌功能和梗死面积的影响

Effect of Ischemic Postconditioning on Myocardial Function and Infarct Size Following Reperfusion Injury in Diabetic Rats Pretreated With Vildagliptin.

作者信息

Bayrami Goltaj, Karimi Pouran, Agha-Hosseini Fariba, Feyzizadeh Saeid, Badalzadeh Reza

机构信息

1 Physiology Laboratory, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

2 Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

J Cardiovasc Pharmacol Ther. 2018 Mar;23(2):174-183. doi: 10.1177/1074248417729881. Epub 2017 Sep 13.

DOI:10.1177/1074248417729881

PMID:28901167

Abstract

BACKGROUND

Cardioprotective actions of ischemic postconditioning (IPostC) against ischemia/reperfusion (I/R) injury are abolished in diabetic hearts. This study has investigated the combined effects of IPostC and vildagliptin (Vilda) on myocardial function and infarct size (IS) against I/R injury in diabetic myocardium.

METHODS

Diabetes was induced by a high-fat diet/low dose of streptozotocin (35 mg/kg; intraperitoneally) in Wistar rats (200-250 g) and lasted for 12 weeks. Vilda (6 mg/kg/d) was orally administered for 5 weeks in diabetic groups after seventh week of diabetes. At the end of the 12-week period, the hearts of rats were removed and subjected to 35-minute regional ischemia (through left anterior descending ligation) followed by 60-minute reperfusion, on Langendorff apparatus. Ischemic postconditioning was induced by 6 repetitive cycles of 10-second ischemia and 10-second reperfusion, immediately at the onset of the reperfusion. Myocardial hemodynamic was measured throughout the experiment. The IS was assessed by triphenyltetrazolium chloride staining method. The myocardial contents of troponin-I (cTnI), interleukin-6 (IL-6), and 8-isoprostane were measured in the homogenate from ischemic zone of left ventricles by enzyme-linked immunosorbent assay kit.

RESULTS

Pretreatment of the diabetic rats with Vilda significantly recovered the diabetes-induced reduction in left ventricular developed pressures and contractility at the baseline ( P < .05 to P < .01). After I/R injury, IPostC could not significantly improve the myocardial function, cTnI content, and IS of the diabetic hearts. However, in Vilda-treated hearts, concomitant application of IPostC significantly recovered the heart functions, returned cTnI content as well as myocardial IL-6 and 8-isoprostane levels back to the control values ( P < .01 to P < .001), and reduced IS more effectively (by 45%) in comparison to the diabetic group ( P < .001).

CONCLUSION

Besides its glycemic and lipid profile controlling effects, Vilda has a protective effect on heart function and tends to restore cardioprotective effects of IPostC on diabetic hearts.

摘要

背景

缺血后处理（IPostC）对缺血/再灌注（I/R）损伤的心脏保护作用在糖尿病心脏中被消除。本研究探讨了IPostC与维格列汀（Vilda）联合应用对糖尿病心肌I/R损伤后心肌功能和梗死面积（IS）的影响。

方法

采用高脂饮食/低剂量链脲佐菌素（35 mg/kg；腹腔注射）诱导Wistar大鼠（200 - 250 g）糖尿病模型，持续12周。糖尿病组在糖尿病第7周后口服Vilda（6 mg/kg/d），持续5周。在12周实验结束时，取出大鼠心脏，在Langendorff装置上进行35分钟的局部缺血（通过结扎左前降支），随后再灌注60分钟。在再灌注开始时立即通过6个重复的10秒缺血和10秒再灌注周期诱导缺血后处理。在整个实验过程中测量心肌血流动力学。通过氯化三苯基四氮唑染色法评估梗死面积。采用酶联免疫吸附测定试剂盒测定左心室缺血区匀浆中心肌肌钙蛋白I（cTnI）、白细胞介素-6（IL-6）和8-异前列腺素的心肌含量。

结果

用Vilda预处理糖尿病大鼠可显著恢复糖尿病诱导的基线时左心室舒张末压和收缩性降低（P <.05至P <.01）。在I/R损伤后，IPostC不能显著改善糖尿病心脏的心肌功能、cTnI含量和梗死面积。然而，在Vilda治疗的心脏中，联合应用IPostC可显著恢复心脏功能，使cTnI含量以及心肌IL-6和8-异前列腺素水平恢复到对照值（P <.01至P <.001），并且与糖尿病组相比更有效地减少梗死面积（降低45%）（P <.001）。