| Objective Remifentanil, a short-acting opioid analgesics,it has been commonly used in clinical anesthesia.Its analgesic effect is strong, work fast, duration time is short, eliminate quickly and it’s without accumulation during a long time infusion. It has been known that on the healthy animal model in vivo, remifentanil postconditioning can produce a strong protective effect on myocardial ischemia reperfusion injury similar to ischemia pre/postconditioning.As one of the most common intercurrent diseases of the cardiovascular disease,diabetes brings lots of specific cardiovascular changes,which can reduce the drug susceptibility to remifentanil postconditioning. Studies have found that both diabetes and high sugar state can weaken the myocardial protection of remifentanil postconditioning in vivo and in vitro. The underlying mechanism may be related to the antiapoptotic and apoptosis protein expression disorders associated with endoplasmic reticulum stress. This study was to research whether endoplasmic reticulum stress is involved in the abolishment of cardioprotection mediated by remifentanil postconditioning in DM rats.Methods Adult male Sprague-Dawley rats,weighing 250~300 g,were used in the study. A model for T1 DM was established by intraperitoneal injection of streptozotoein 50 mg/kg and was confirmed by blood glucose≥16.7 mmol/L. Thirty six T1 DM rats were randomly divided into 3 groups(n=12 each):DM sham operation group(DM-S group);DM ischemia- reperfusion(I/R) group( DM-IR group) and DM remifentanil postconditioning group(DM-RE group). Another thirty six nondiabetic mellitus ratswere also randomly divided into 3 group(n=12 each): nondiabetic mellitus sham operation group(NDM-S group); nondiabetic mellitus I/R group(NDM-IR group) and nondiabetic mellitus remifentanil postconditioning group(NDM-RE group). Myocardial I/R injury was induced 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 5 min before reperfusion. NDM-IR and DM-IR group were treated with saline for comparison. MAP,SBP,HR and RPP(HR×SBP) were recorded before ischemia,30 min of ischemia and 120 min of reperfusion.Six rats were chosen from each group at 120 min of reperfusion,their arterial blood samples were collected for measurement of plasma cardiac troponin I(c Tn I) concentration.The animals were then sacrificed for determination of total areas of right and left ventricles(LV+RV), infarct area(IS),area at risk(AAR) and IS/AAR.The left six rats from each group were sacrificed at 120 min of reperfusion,their left ventricular apex was used to detect the expression of endoplasmic reticulum stress related molecular marker by Western blot, such as glucose regulated protein 78(GRP78),C/EBP homologous protein(CHOP) and caspase-12.Results Characteristic of rats: After 2 weeks of a single dose of streptozotocin, diabetic rats had significantly higher levels of plasma glucose than the non-diabetic rats(p < 0.05). Heart weight and body weight were lower in the diabetic group than in the non-diabetic group(p < 0.05).Hemodynamic parameters: There is no statistical significance in HR of each group.(P > 0.05).Compared with NDM-S group,MAP and RPP were decreased in the NDM-I/R group(P < 0.05).Compared with NDM-IR group,MAP and RPP were increased in the NDM-RE group(p < 0.05).Compared with DM-S group,MAP and RPP were decreased in the DM-I/R group and DM-RE group(p < 0.05).Compared with NDM-RE group,MAP and RPP were decreased in the DM-RE group(P < 0.05).At the moment of T1,MAP and RPP were decreased in group NDM-I/R,DM-I/R and DM-RE.Myocardial Infarct Size and c Tn I: Compared withNDM-S group,IS/ARR and concentration of c Tn I were significantly increased in the I/R group(P < 0.05).Compared with NDM-IR group,IS/ARR and concentration of c Tn I were decreased in the NDM-RE group(P < 0.05). Compared with DM-S group,both IS/ARR and concentration of c Tn I were decreased in the DM-I/R group and DM-RE group(P < 0.05).Compared with NDM-RE group,IS/AAR and concentration of c Tn I were higher in the DM-RE group(P < 0.05).Western blot analysis: Compared with NDM-S group,the level of GRP78,CHOP and caspase-12 were up-regulated in the I/R group(P < 0.05).Compared with NDM-IR group,the level of GRP78,CHOP and caspase-12 were down-regulated in the NDM-RE group(P < 0.05). Compared with DM-S group,the expression of all the proteins were decreased in the DM-I/R group and DM-RE group(P < 0.05).Compared with NDM-RE group,the level of GRP78,CHOP and caspase-12 were higher in the DM-RE group(P < 0.05).However,there is no statistical significance in each parameter between DM-IR group and DM-RE group(P > 0.05).Conclusion Endoplasmic reticulum stress is involved in the abolishment of cardioprotection mediated by remifentanil postconditioning in DM rats. |
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