Abstract
BackgroundDiabetes mellitus has multiple complications including neuropathy and increases cardiovascular events. Paeoniflorin (PF), a monoterpene glycoside, plays an essential role in neuroprotection and ischemic heart disease. In this study, we aimed to investigate the hypothesis that PF protects mice with diabetes mellitus against myocardial ischemic injury, and determine its associated mechanisms.ResultsMyocardial infarction (MI) was generated in the streptozotocin-mediated diabetic mice, which were pretreated with either vehicle or PF, respectively. Myocardial infarct size, myocardial enzyme, cardiac function, circulating calcitonin gene-related peptide (CGRP) concentration, histological analysis and the expression of associated molecules were determined and compared among different experimental groups. Compared to diabetic hearts pretreated with vehicle, hearts pretreated with PF exhibited less tissue damage and better CGRP concentration in serum when subjected to myocardial ischemia. Transient receptor potential vanilloid 1(TRPV1) gene knockout attenuated PF-mediated cardioprotection. Moreover, a specific Ca2+/calmodulin-dependent protein kinase (CaMK) inhibitor, KN-93, increased tissue damage and decreased CGRP activity in serum. Meanwhile, pretreated with PF increased the phosphorylation of cAMP response element binding protein (CREB).ConclusionsTaken together, these findings demonstrate that PF protects diabetic mice against MI at least partially via the TRPV1/CaMK/CREB/CGRP signaling pathway.
Highlights
Diabetes mellitus has multiple complications including neuropathy and increases cardiovascular events
calcitonin gene-related peptide (CGRP) levels remarkably increased in each group subjected to ischemia; which peaked at 6 h after Myocardial infarction (MI) (P < 0.05)
These results indicate that pretreatment with PF significantly elevates the concentration of CGRP in plasma, which is a protective factor for diabetic hearts against MI-induced injury
Summary
Diabetes mellitus has multiple complications including neuropathy and increases cardiovascular events. We aimed to investigate the hypothesis that PF protects mice with diabetes mellitus against myocardial ischemic injury, and determine its associated mechanisms. DM is characterized by increased plasma glucose levels and is often accompanied by several complications including microangiopathy, neuropathy and mobilopathy, which lead to high morbidity and mortality [3,4,5]. Previous studies have indicated that TRPV1 and its main neuropeptides calcitonin gene-related peptide (CGRP) and substance P significantly decreased in diabetic hearts, which was related to the poor recovery of cardiac function after. CGRP, the major neuropeptide released from nerve terminals, has both positive inotropic and potent vasodilatory effects which lead to augment post-ischemic cardiac performance [12]. Preconditioning with CGRP protected against ischemia/reperfusion (I/R) injury in isolated hearts of rats [11]
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