scholarly journals Combination of metformin and p38 MAPK inhibitor, SB203580, reduced myocardial ischemia/reperfusion injury in non‑obese type 2 diabetic Goto‑Kakizaki rats

2019 ◽  
Author(s):  
Jantira Sanit ◽  
Eakkapote Prompunt ◽  
Punyanuch Adulyaritthikul ◽  
Nuttikarn Nokkaew ◽  
Podsawee Mongkolpathumrat ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion Injury ◽  
P38 Mapk Inhibitor ◽  
Myocardial Ischemia Reperfusion ◽  
Type 2 Diabetic ◽  
Mapk Inhibitor

scholarly journals 5′-N-Ethylcarboxamido Adenosine Attenuates Myocardial Ischemia/Reperfusion Injury In Type 2 Diabetic Rats Through A2AR/PKCα/miR-15a Signaling

2021 ◽  
Author(s):  
Chao Chen ◽  
Jianjuan Ke ◽  
Huang Ding ◽  
Chengjun Hu ◽  
Zhenggang Wang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Rat ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Type 2 Diabetic

Abstract Background/aims: Type 2 diabetes mellitus aggravates myocardial ischemia/reperfusion injury (MI/RI). Activation of adenosine receptors (ARs) confer to attenuated MI/RI in nondiabetic animals and human. However, this effects and mechanism of ARs in the type 2 diabetic state are still unknown. In present study, we established a type 2 diabetic rat in vivo myocardial ischemia/reperfusion (MI/R) model to evaluate the effect of ARs on MI/RI with a focus on the A2A adenosine receptor (A2 AR) -mediated cardioprotective effects. Methods: Type 2 diabetic rat were subjected to myocardial infarction by LAD ligation in situ and randomly received ARs agonist and/or antagonists or vehicle treatment. After 2h marker of the extent of myocardial damage(ejection fraction of the LV, Infarct size, plasma cardiac troponin I) were measured and pro- and anti-apoptotic signals (protein kinase Cα，Bcl-2, Bax, miR-15), and marker of apoptosis execution (cleaved caspase-3, TUNEL) were quantified in the infarcted myocardium.Results: non-selective adenosine receptor agonist 5′-(N-ethylcarboxamido) adenosine treatment attenuates MI/RI, improve post-MI/R left ventricular function, limit infarct size, reduce cardiac troponin I release, reduce myocardial apoptosis, up-regulates bcl2 and down-regulates miR-15a, bax and cleaved caspase-3 expression; This protective effects were attenuated by pretreatment with selective A2AR antagonist ZM241385 or PKCα-selective inhibitor Go6976; and duplicated by treatment with A2AR-selective agonist CGS21680 or PKCα-potent activator PMA.Conclusions: NECA reduces MI/RI in T2DM rats via the A2AR/PKCα/miR-15a signaling pathway; NECA is a useful target candidate for the treatment of MI/RI in patient with type 2diabetes.

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