Effects of Dexmedetomidine Postconditioning on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Role of the PI3K/Akt-Dependent Signaling Pathway

• Published in: Journal of Diabetes Research Vol. 2018; no. 2018; pp. 1 - 10
• Main Authors: Li, Zhenghong, Li, Xiaohong, Ye, Hongwei, Wang, Ya, Hu, Jing, Cheng, Xiangyang, Gao, Qin
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2018; Hindawi; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Animals; Antibodies; Apoptosis; Care and treatment; Complications and side effects; Dexmedetomidine - pharmacology; Diabetes; Diabetes Mellitus, Experimental - metabolism; Glycogen Synthase Kinase 3 beta; Heart; Heart - drug effects; Heart diseases; Hyperglycemia; Insulin resistance; Ischemia; Ischemic Postconditioning - methods; Kinases; Laboratory animals; Male; Medical research; Medicine, Experimental; Myocardial Ischemia - drug therapy; Myocardial Ischemia - metabolism; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - metabolism; Myocardium - metabolism; Oxidative stress; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Risk factors; Rodents; Signal Transduction - drug effects; Type 2 diabetes; Veins & arteries; United States > US; China
• DOI: 10.1155/2018/3071959
• ISSN: 2314-6745; 2314-6753

Objective. The present study was designed to determine whether dexmedetomidine (DEX) exerts cardioprotection against myocardial I/R injury in diabetic hearts and the mechanisms involved. Methods. A total of 30 diabetic rats induced by high-glucose-fat diet and streptozotocin (STZ) were randomly assigned to five groups: diabetic sham-operated group (DM-S), diabetic I/R group (DM-I/R), diabetic DEX group (DM-D), diabetic DEX + Wort group (DM-DW), and diabetic Wort group (DM-W). Another 12 age-matched male normal SD rats were randomly divided into two groups: sham-operated group (S) and I/R group (I/R). All rats were subjected to 30 min myocardial ischemia followed by 120 min reperfusion except sham groups. Plasmas were collected to measure the malondialdehyde (MDA), creatine kinase isoenzymes (CK-MB), and lactate dehydrogenase (LDH) levels and superoxide dismutase (SOD) activity at the end of reperfusion. Pathologic changes in myocardial tissues were observed by H-E staining. The total and phosphorylated form of Akt and GSK-3β protein expressions were measured by western blot. The ratio of Bcl-2/Bax at mRNA level was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results. DEX significantly reduced plasma CK-MB, MDA concentration, and LDH level and increased SOD activity caused by I/R. The phosphorylation of Akt and GSK-3β was increased, Bcl-2 mRNA and the Bcl-2/Bax ratio was increased, and Bax mRNA was decreased in the DEX group as compared to the I/R group, while posttreatment with Wort attenuated the effects induced by DEX. Conclusion. The results of this study suggest that DEX postconditioning may increase the phosphorylation of GSK-3β by activating the PI3K/Akt signaling pathway and may inhibit apoptosis and oxidative stress of the myocardium, thus exerting protective effects in diabetic rat hearts suffering from I/R injury.