Relationship between endoplasmic reticulum stress and diabetes mellitus-caused influence on cardioprotection induced by remifentanil postconditioning in rats

Abstract

Objective To evaluate the relationship between endoplasmic reticulum stress and diabetes mellitus(DM)-caused influence on cardioprotection induced by remifentanil postconditioning in rats. Methods Adult male Sprague-Dawley rats, weighing 250-300 g, were used in the study.A model for type 1 DM was established by intraperitoneal streptozotocin 50 mg/kg and confirmed by blood glucose ≥ 16.7 mmol/L.Thirty six rats with type 1 DM were randomly divided into 3 groups (n = 12 each) using a random number table: sham operation group (DM-S group), myocardial ischemia-reperfusion (I/R) group (DM-I/R group) and remifentanil postconditioning group (DM-R group). Another 36 normal rats were exposed to single intraperitoneal injection of sodium citrate-hydrochloric acid buffer solution and served as control group.Two weeks later 36 normal rats with nondiabetes mellitus were also randomly divided into 3 groups (n = 12 each) using a random number table: sham operation group (NDM-S group), myocardial I/R group (NDM-I/R group) and remifentanil postconditioning group (NDM-R group). Myocardial I/R was produced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion.Remifentanil postconditioning was induced by 10 min infusion of remifentanil 10 μg·kg-1·min-1 via the femoral vein starting from 5 min before reperfusion.Before ischemia and at 30 and 120 min of ischemia, MAP, SP and HR were recorded and rate-pressure product (RPP) was calculated.At 120 min of reperfusion, arterial blood samples were collected for measurement of plasma cardiac troponin I (cTnI) concentration.The animals were then sacrificed and hearts were removed for determination of myocardial infarct size (IS). The left 6 rats from each group were sacrificed at 120 min of reperfusion, the specimens from their left ventricular apex were obtained to detect the expression of endoplasmic reticulum stress marker glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and caspase-12 by Western blot. Results MAP and RPP were significantly decreased, the plasma concentration of cTnI was increased, changes of cardiac infarction were found, and the expression of GRP78, CHOP and caspase-12 was up-regulated in diabetic and nondiabetic rats.Remifentanil postconditioning could inhibit the expression of GRP78, CHOP and caspase-12, increase MAP and RPP, decrease the plasma concentration of cTnI, and reduce myocardial infarct size in nondiabetic rats, but it had no such effects in the diabetic rats.The expression of GRP78, CHOP and caspase-12 was significantly higher after remifentanil postconditioning in diabetic rats than in nondiabetic rats. Conclusion Enhanced endoplasmic reticulum stress is involved in DM-caused loss of cardioprotection induced by remifentanil postconditioning in rats. Key words: Diabetes mellitus; Piperidines; Endoplasmic reticulum; Stress; Myocardial reperfusion injury