Post-Ischemic Treatment of Recombinant Human Secretory Leukocyte Protease Inhibitor (rhSLPI) Reduced Myocardial Ischemia/Reperfusion Injury

Biomedicines

Nipon Chattipakorn¹  Aussara Panya²  Anusak Kijtawornrat³  Podsawee Mongkolpathumrat⁴  Sarawut Kumphune⁴  Stephanie Barrère-Lemaire⁵  Eakkapote Prompunt⁶ 

[1] Cardiac Electrophysiology Research and Training Centre, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand;Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand;Department of Physiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand;Graduate Programs in Biomedical Sciences, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand;Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, Inserm, 141, Rue de la Cardonille, 34094 Montpellier, France;Unit of Excellence in Infectious Disease, Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao 56000, Thailand;

关键词: ischemic heart disease;    ischemia/reperfusion injury;    secretory leukocyte protease inhibitor (SLPI);    cardioprotection;    post-ischemic treatment;   

DOI  :  10.3390/biomedicines9040422

来源: DOAJ

【 摘 要 】

Myocardial ischemia/reperfusion (I/R) injury is a major cause of mortality and morbidity worldwide. Among factors contributing to I/R injury, proteolytic enzymes could also cause cellular injury, expand the injured area and induce inflammation, which then lead to cardiac dysfunction. Therefore, protease inhibition seems to provide therapeutic benefits. Previous studies showed the cardioprotective effect of secretory leukocyte protease inhibitor (SLPI) against myocardial I/R injury. However, the effect of a post-ischemic treatment with SLPI in an in vivo I/R model has never been investigated. In the present study, recombinant human (rh) SLPI (rhSLPI) was systemically injected during coronary artery occlusion or at the onset of reperfusion. The results show that post-ischemic treatment with rhSLPI could significantly reduce infarct size, Lactate Dehydrogenase (LDH) and Creatine kinase-MB (CK-MB) activity, inflammatory cytokines and protein carbonyl levels, as well as improving cardiac function. The cardioprotective effect of rhSLPI is associated with the attenuation of p38 MAPK phosphorylation, Bax, caspase-3 and -8 protein levels and enhancement of pro-survival kinase Akt and ERK1/2 phosphorylation. In summary, this is the first report showing the cardioprotective effects against myocardial I/R injury of post-ischemic treatments with rhSLPI in vivo. Thus, these results suggest that SLPI could be used as a novel therapeutic strategy to reduce myocardial I/R injury.

【 授权许可】

Unknown