内质网应激与糖尿病因素影响大鼠瑞芬太尼后处理心肌保护作用的关系  

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

作　　者：朱冰青[1] 陈立建[1] 章雨雯 陈满丽[1] 张雷[1] 顾尔伟[1] 

机构地区：[1]安徽医科大学第一附属医院麻醉科,合肥市230022

出　　处：《中华麻醉学杂志》2015年第3期347-351,共5页Chinese Journal of Anesthesiology

基　　金：基金项目：国家自然科学基金专项主任基金研究项目（81341014）;安徽省自然科学基金（1308085MH118）

摘　　要：目的探讨内质网应激与糖尿病因素影响大鼠瑞芬太尼后处理心肌保护作用的关系。方法健康成年雄性sD大鼠，体重250—300g，采用腹腔注射链脲佐菌素50mg／kg的方法制备1型糖尿病模型。取糖尿病模型制备成功的大鼠36只，采用随机数字表法，将其分为3组（n=12）：假手术组（DM—S组）、心肌缺血再灌注组（DM—IR组）和瑞芬太尼后处理组（DM—R组）。另取正常大鼠36只，腹腔注射柠檬酸钠缓冲液50mg／kg作为对照。2周后，采用随机数字表法分为3组（n=12）：假手术组（NDM．S组）、心肌缺血再灌注组（NDM一1R组）和瑞芬太尼后处理组（NDM—R组）。采用结扎左冠状动脉前降支30min，再灌注120min的方法建立大鼠心肌缺血再灌注损伤模型。NDM—R组和DM—R组于再灌注前5min经股静脉输注瑞芬太尼10μg·kg^-1·min。持续10min。于缺血前、缺血30min和再灌注120min时记录MAP、SP和HR，计算心率收缩压乘积（RPP）。于再灌注120min时取颈动脉血样，测定血浆eTnI浓度，处死大鼠后取心脏，计算心肌梗死体积；取心尖部组织，采用West—ernblot法检测内质网应激相关分子葡萄糖调节蛋白78（GRP78）、C／EBP环磷酸腺苷反应元件结合转录因子同源蛋白（CHOP）和caspase-12的表达水平。结果非糖尿病与糖尿病大鼠心肌缺血再灌注时MAP和RPP降低，血浆cTnI浓度升高，心肌发生梗死样改变，心肌组织GRP78、CHOP和caspase-12表达上调。瑞芬太尼后处理可抑制非糖尿病大鼠心肌缺血再灌注时心肌组织GRP78、CHOP和caspase-12的表达，升高MAP和RPP，降低血浆cTnI浓度，减小心肌梗死体积，但对糖尿病大鼠无此作用。瑞芬太尼后处理后糖尿病大鼠心肌缺血再灌注时心肌组织GRP78、CHOP和caspase-12的表达水平高于非糖尿病大鼠。结论糖尿病因素取消大鼠瑞芬太尼后处理心肌保护作用与内质网应激水平增强有关Objective To evaluate the relationship between endoplasmic reticulum stress and dia- betes 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 mmoi/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 ex- posed to single intraperitoneal injection of sodium citrate-hydrochloric acid buffer solution and served as con- trol 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 ~g ~ kg-1 ~ rain-~ 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 myo- cardial 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 （G

关 键 词：糖尿病 哌啶类 内质网 应激 心肌再灌注损伤 

分 类 号：R614[医药卫生—麻醉学]