Nicorandil Protect the Myocardium from Ischemia Reperfusion Injury through Inhibiting Endoplasmic Reticulum Stress in Rats
Ye Ming
Wu Hui
Abstract：Objective To observe the effect of nicorandil preconditioning on rat in vitro myocardial ischemia reperfusion(I/R)injury and the expression of the key factors in endoplasmic reticulum stress signal pathway.Methods Forty-eight Sprague-Dawley (SD) rats were randomly divided into six groups:balance group,balance+100 μmol/L nicorandil preconditioning group,I/R control group,30 μmol/L nicorandil preconditioning group,100 μmol/L nicorandil preconditioning group and 300 μmol/L nicorandil preconditioning group.Hearts from each group were excised and subjected to 30 min global ischemia followed by 120 min reperfusion in a Langendorff apparatus.Homodynamic parameters of left ventricular (LV) were recorded and evaluated with Powerlab system,including LV developed pressure (LVDP),LV end-diastolic pressure (LVEDP),and the derivative of left ventricular(+dP/dtmax and-dP/dtmax).Cell death was reflected by lactate dehydrogenase (LDH) activity assay in coronary effluent.Cardiac infarct size was also measured after nicorandil treatment by Triphenyl Tetrazolium Chloride (TTC) staining.The mRNA levels of ER stress markers,including glucose-regulated protein (GRP) 78 and C/-EBP homologous protein (CHOP) were examined by real time-PCR.The protein expressions of GRP78 and CHOP were detected by western blot.Results Nicorandil preconditioning improved post-ischemic cardiac function of isolated rat heart in a concentration dependent manner,and reduced LDH activity in coronary effluent.Consistent with the above observation,nicorandil preconditioning significantly reduced the infarct size after ischemia reperfusion.The mRNA level and protein expression of GRP78 and CHOP were upregulated in I/R heart.When the I/R hearts were treated with nicorandil,both CHOP and GRP78 levels were significantly attenuated,which emerged in an dose-dependent way.Conclusion Nicorandil preconditioning could alleviate myocardial I/R injury,ameliorate post-ischemic contractile function recovery,and inhibit endoplasmic reticulum stress induced by myocardial I/R in a dose-dependent manner in vivo.
Keywords：ischemia reperfusion injurynicorandilmyocardiumleft ventricular end-diastolic pressurethe derivative of left ventricularheart ratelactate dehydrogenaseglucose-regulated protein 78C/-EBP homologous protein
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 1310-1314 )