[Protective effect of ischemia and diazoxide preconditioning on postischemic reperfused myocardium and possible mechanism thereof].

Abstract

OBJECTIVE:

To study the protective mechanism of ischemic preconditioning (IPC) and diazoxide preconditioning (DPC) against myocardium ischemia-reperfusion (I/R) injury.

METHODS:

The hearts were taken out from 30 male Wistar rats and were divided randomly into 3 equal groups: I/R group undergoing 30-min equilibration perfusion and 30-min ischemia and then 60-min reperfusion, IPC group undergoing 10-min equilibration perfusion and then two cycles of 5 min ischemia interspersed with 5 min reperfusion prior to 30 min ischemia and a 60-min reperfusion, and DPC group undergoing 10-min equilibration perfusion and 2 cycles of 5 min of 100 microM diazoxide perfusion followed by 5-min drug-free period before the 30 min ischemia and 60-min reperfusion. Frozen sections of myocardium at the cardiac apex were made and immunohistochemical staining was used to detect the expression of peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha). Ultrathin sections 70 nm thick were made and transmission electron microscopy was used to detect the structure of the mitochondria with the Flameng scoring system.

RESULTS:

The PGC-1alpha expression of the IPC and DPC groups were significantly higher than that of the I/R group (P<0.01 and P<0.05), however, there was no significant difference in PGC-1alpha is expression between the IPC and DPC groups (P >0.05). The Flameng scores of the IPC and DPC groups were 0.44 +/- 0.13 and 0.47 +/- 0.10 respectively, both significantly higher than that of the I/R group (1.78 +/- 0.14, both P <0.01), however, there was no significant difference between IPC and DPC groups (P>0.05).

CONCLUSION:

IPC and DPC can protect myocyte mitochondria from the injury of ischemia/ reperfusion. The cardioprotective effects of IPC and DPC may be concerned with the activation and high expression of PGC-1alpha.

• Authors: Jin-Song Han, De-Min Yan, Zeng-Wei Wang, Hong-Yu Zhu
• Journal: Zhonghua yi xue za zhi (Zhonghua Yi Xue Za Zhi) Vol. 88 Issue 8 Pg. 555-8 (Feb 26 2008) ISSN: 0376-2491 [Print] China
• PMID: 18649773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Ppargc1a protein, rat
• RNA-Binding Proteins
• Transcription Factors
• Vasodilator Agents
• Peroxidase
• Diazoxide

Topics

• Animals
• Diazoxide (therapeutic use)
• Immunohistochemistry
• Ischemia (complications)
• Ischemic Preconditioning, Myocardial (methods)
• Male
• Microscopy, Electron, Transmission
• Mitochondria, Heart (drug effects, metabolism, ultrastructure)
• Myocardial Reperfusion Injury (etiology, metabolism, prevention & control)
• Myocardium (metabolism)
• Peroxidase (metabolism)
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• RNA-Binding Proteins
• Rats
• Rats, Wistar
• Transcription Factors (metabolism)
• Vasodilator Agents (therapeutic use)