Alfentanil pretreatment exerts protective effects on myocardial ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress
Objective To explore the effect of alfentanil pretreatment on protecting myocardial ischemia-reperfusion injury(MIRI)in rats and the underlying mechanism.Methods Sixty male Sprague-Dawley(SD)rats were randomly divided into sham group,MIRI group,low-dose alfentanil pretreatment group(3 mg/kg)and high-dose alfentanil pretreatment group(6mg/kg),with 15 rats per group.Except for rats in sham group,the MIRI modeling was performed in the remaining groups.Cardiac function indicators,including the left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF)and fractional shortening(LVFS)were compared.Myocardial damage indicators,including creatine kinase myocardial band(CK-MB)and cardiac troponin Ⅰ(cTnⅠ)were compared.The area of cardiomyocyte infarction,myocardial damage and apoptosis in rats were detected by dual staining,hematoxylin and eosin(H&E)staining and terminal deoxy nucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining,respectively.Endoplasmic reticulum(ER)stress proteins,including glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP)and family with sequence similarity 134,member B(FAM134B)in rat myocardium were detected by immunofluorescence and Western blot.Results Compared with those of sham group,rats in the MIRI group had significantly higher LVEDD,LVESD,CK-MB,cTnⅠ,proportion of cardiomyocyte infarcted size,myocardial apoptosis,and immunofluorescence intensities and protein levels of GRP78 and CHOP,and significantly lower LVEF,LVFS,and immunofluorescence intensity and protein level of FAM134B(P＜0.05).Compared with those of MIRI group,rats in the low-dose alfentanil pretreatment group and high-dose alfentanil pretreatment group had significantly lower LVEDD,LVESD,CK-MB,cTnⅠ,proportion of cardiomyocyte infarcted size,myocardial apoptosis,and immunofluorescence intensities and protein levels of GRP78 and CHOP,and significantly higher LVEF,LVFS,and immunofluorescence intensity and protein level of FAM134B(P＜0.05).Compared with those of the low-dose alfentanil pretreatment group,rats in the high-dose alfentanil pretreatment group had significantly lower LVEDD,LVESD,CK-MB,cTnⅠ,proportion of cardiomyocyte infarcted size,myocardial apoptosis,and immunofluorescence intensities and protein levels of GRP78 and CHOP,and significantly higher LVEF,FS,and immunofluorescence intensity and protein level of FAM134B in a dose-dependent manner(P＜0.05).Conclusion Alfentanil pretreatment dose-dependently alleviates pathological damages in myocardium,reduces the area of cardiomyocyte infarction and inhibits cardiomyocyte apoptosis in rats with MIRI by inhibiting ER stress.
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