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Poly (ADP-ribose) synthetase inhibitor has a heart protective effect in a rat model of experimental sepsis
Lianshuang Zhang1, Jinpeng Yao2, Xifeng Wang3
1Department of Histology and Embryology, Binzhou Medical College Yantai, P. R. China.
Unlabelled:
The aim of this study is to investigate whether PARP inhibitor could reduce cell apoptosis and injury in the heart during sepsis.
Materials And Methods:
60 healthy male Sprague-Dawley (SD) rats were randomly divided into 4 groups---sham group, modal group, 3-AB pretreatment group and 3-AB treatment group, 15 rats per group. The cecal ligation and puncture (CLP) model of sepsis was used. The following were determined--levels of malondialdehyde (MDA), ATP and nicotinamide adenine dinucleotide (NAD+), expression of PARP, Bcl-2, Bax, cytochrome C and caspase 3 activity in the myocardium tissue, levels of serum creatine kinase muscle brain (CK-MB) fraction and troponin I.
Results:
Histological and molecular analyses showed that myocardial cells apoptosis were associated with mitochondria injury, with an increase in the amount of PARP and a decrease in ATP and NAD+ levels in model group. In addition, the levels of Bax, cytochrome C and caspase 3 activity, serum levels of CK-MB and troponin I increased, but levels of Bcl-2 significantly decreased. Inhibition of PARP upregulated the levels of ATP, NAD + and Bcl-2, and significantly reduced the activation of PARP and caspase 3, decreased the levels of MDA, cytochrome C, CK-MB and troponin I. As a result, apoptosis in the heart was attenuated.
Conclusion:
These results indicate that PARP activation may be involved in apoptosis in the heart induced by sepsis and 3-AB could improve it.
