Role of endoplasmic reticulum stress in myocardial ischemia-reperfusion injury in rats: relationship with autophagy / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of endoplasmic reticulum stress in myocardial ischemia-reperfusion (I/R) injury and the relationship with autophagy in rats.Methods:Thirty-six healthy adult male Sprague-Dawley rats, weighing 250-300 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (Sham group), myocardial I/R group (IR group), and endoplasmic reticulum stress inhibitor 4-PBA group (PBA group). Myocardial I/R was produced by occlusion of left anterior descending branch of coronary artery for 30 min followed by reperfusion for 120 min.Sham group only underwent thoracotomy without block of left anterior descending branch of coronary artery.Endoplasmic reticulum stress inhibitor 4-PBA 500 mg·kg -1·d -1 was given intragastrically for 3 consecutive days before the I/R model was developed in PBA group, while the equal volume of normal saline was given instead in Sham and IR groups.The blood samples from the iliac vein were collected at 120 min of reperfusion for determination of the plasma creatine kinase isoenzymes (CK-MB) and cardiac troponin I (cTnI) concentrations (by enzyme-linked immunosorbent assay). The rats were then sacrificed, and myocardial tissues were removed for detection of myocardial glucose-regulated protein 78 (GRP78) and microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) and autophagy-related protein 5 (ATG5) expression (by Western blot). Result:Compared with Sham group, the concentrations of CK-MB and cTnI in plasma were significantly increased in IR and PBA groups, the expression of GRP78, ATG5 and LC3Ⅱ was up-regulated, and the pathological damage was aggravated in IR group ( P<0.05). Compared with IR group, the concentrations of CK-MB and cTnI in plasma were significantly decreased, the expression of GRP78, ATG5 and LC3Ⅱ was down-regulated ( P<0.05), and the pathological changes were significantly attenuated in PBA group. Conclusion:Endoplasmic reticulum stress is involved in the process of myocardial I/R injury, and the mechanism may be related to promotion of autophagy in rats.