Effects of Dexmedetomidine Postconditioning on Myocardial IschemiaReperfusion Injury in Diabetic Rats: Role of the PI3KAkt-Dependent Signaling Pathway

Abstract EN

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.