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

Abstract

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.

• Authors: Xiangyang Cheng, Jing Hu, Ya Wang, Hongwei Ye, Xiaohong Li, Qin Gao, Zhenghong Li
• Journal: Journal of diabetes research (J Diabetes Res) Vol. 2018 Pg. 3071959 ( 2018) ISSN: 2314-6753 [Electronic] England
• PMID: 30402501 (Publication Type: Journal Article)

Chemical References

• Dexmedetomidine
• Phosphatidylinositol 3-Kinases
• Glycogen Synthase Kinase 3 beta
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Dexmedetomidine (pharmacology)
• Diabetes Mellitus, Experimental (metabolism)
• Glycogen Synthase Kinase 3 beta
• Heart (drug effects)
• Ischemic Postconditioning (methods)
• Male
• Myocardial Ischemia (drug therapy, metabolism)
• Myocardial Reperfusion Injury (drug therapy, metabolism)
• Myocardium (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)