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2018 ; 2018
(ä): 2750695
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Polydatin Protects Diabetic Heart against Ischemia-Reperfusion Injury via
Notch1/Hes1-Mediated Activation of Pten/Akt Signaling
#MMPMID29636838
Yu L
; Li Z
; Dong X
; Xue X
; Liu Y
; Xu S
; Zhang J
; Han J
; Yang Y
; Wang H
Oxid Med Cell Longev
2018[]; 2018
(ä): 2750695
PMID29636838
show ga
Diabetes exacerbates oxidative/nitrative stress during myocardial
ischemia-reperfusion (MI/R) injury. Recent studies highlighted the
cardioprotective actions of polydatin. However, its effect on diabetic MI/R
injury and the underlying mechanisms remain unknown. This work was undertaken to
evaluate the effect of polydatin on diabetic MI/R injury with a focus on
Notch1/Hes1 signaling and myocardial oxidative/nitrative stress. Streptozotocin-
(STZ-) induced diabetic rats were administered with polydatin (20?mg/kg/d) in the
absence or presence of DAPT (a ?-secretase inhibitor) or LY294002 (a PI3K/Akt
inhibitor) and then subjected to MI/R injury. Polydatin administration preserved
cardiac function and reduced myocardial infarct size. Moreover, polydatin
ameliorated myocardial oxidative/nitrative stress damage as evidenced by
decreased myocardial superoxide generation, malondialdehyde, gp91 (phox)
expression, iNOS expression, NO metabolite level, and nitrotyrosine content and
increased eNOS phosphorylation. However, these effects were blocked by DAPT
administration. DAPT also inhibited the stimulatory effect of polydatin on the
Notch1/Hes1-Pten/Akt signaling pathway in a diabetic myocardium. Additionally,
LY294002 not only abolished polydatin's antiapoptotic effect but also reversed
its inhibitory effect on myocardial oxidative/nitrative stress. Polydatin
effectively reduced MI/R injury and improved left ventricular functional recovery
under diabetic condition by ameliorating oxidative/nitrative stress damage.
Importantly, Notch1/Hes1-mediated activation of Pten/Akt signaling played a
crucial role in this process.
|Animals
[MESH]
|Apoptosis/drug effects
[MESH]
|Biomarkers/metabolism
[MESH]
|Cardiotonic Agents/pharmacology/*therapeutic use
[MESH]