Preconditioning with endoplasmic reticulum stress induced by low dose tunicamycin attenuates myocardial inflammation in myocardial ischemia-reperfusion injury

Abstract

Objective To evaluate the protective effects of preconditioning with endoplasmic reticulum stress (ERS) induced by tunicamycin (TM) against myocardial inflammation in myocardial ischemia reperfusion (I/R) injury. Methods Forty Sprague-Dawley rats were randomly divided into four groups: Sham, TM, I/R, and TM+ I/R. The model of I/R were established by occlusion of the left anterior descending coronary artery for 0.5 h followed by reperfusion for 2 h in I/R group and TM+ I/R group. TM group and TM+ I/R group were treatmented by TM 0.6 mg/kg at 30 min before model established. Blood samples were withdrawn from carotid artery after thoracotomy and 2 h after reperfusion, to detect the levels of creatine kinase isozyme (CK-MB) and lactic dehydrogenase (LDH). The protein expression of cysteinyl aspartate-specific protease (Caspase)-12 and nuclear factor (NF)-κB p65 in heart at the end of the I/R were examined by Western blotting in all groups. The myocardial apoptosis index (AI) using terminal deoxynucleotidyl nick-end labeling were observed in all groups. Results The levels of CK-MB and LDH, AI, and expressions of Caspase-12 and NF-κBp65 protein in I/R group [(546±69) U/L, (2 094±328) U/L, (29.4±3.1)%, 0.461±0.046, and 0.287±0.032 respectively] and TM+ I/R group [(977±103) U/L, (3 198±417) U/L, (12.8±1.9)%, 0.269±0.041, and 0.153±0.031 respectively] were higher than Sham group [(559±81) U/L, (2 459±231) U/L, (2.4±0.3)%, 0.067±0.009, and 0.049±0.006 respectively] and TM group [(572±81) U/L, (2 335±241) U/L, (7.7±0.6)%, 0.149±0.031, and 0.082±0.010 respectively] at 2 h after reperfusion (P<0.05). All observed indexes in I/R group were higher than TM+ I/R group at 2 h after reperfusion(P<0.05). Conclusion Preconditioning with ERS induced by low dose TM attenuates myocardial inflammatory, which may be associated with the reduced I/R injury in rats. Key words: Myocardial ischemia reperfusion injury; Endoplasmic reticulum stress; Preconditioning; Inflammation