Relationship between endoplasmic reticulum stress and diabetes mellitus-caused influence on cardio-protection induced by remifentanil postconditioning in rats / 中华麻醉学杂志

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 tablesham 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 tablesham 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.