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目的:评价胰高血糖素样肽-1受体(GLP-1R)信号通路在七氟烷后处理减轻大鼠心肌缺血再灌注损伤中的作用。方法:SPF级健康雄性SD大鼠80只，8~10周龄，体重300~340 g，采用随机数字表法分为4组(n n＝20)：假手术组(S组)、心肌缺血再灌注组(I/R组)、心肌缺血再灌注+七氟烷后处理组(ISP组)、心肌缺血再灌注+七氟烷后处理+GLP-1R拮抗剂组(ISPE组)。采用结扎冠状动脉左前降支40 min、再灌注2 h的方法制备大鼠心肌缺血再灌注损伤模型。ISP组于再灌注即刻吸入2.4%七氟烷15 min；ISPE组于造模前28 d时开始，腹腔注射GLP-1R拮抗剂Exendin9-39 50 μg/kg(溶于1 ml 0.9%生理盐水中)，1次/d，并于吸入七氟烷前40 min时最后腹腔注射1次，其余处理同ISP组。再灌注结束即刻采集腹主动脉血样，检测血清肌酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH)水平；然后处死大鼠取心脏，采用HE染色法于光镜下观察心肌组织病理学结果，透射电镜下观察心肌细胞超微结构；TTC染色法测定心肌梗死体积，免疫组化染色法检测心肌GLP-1R表达；Western blot法检测心肌GLP-1R、环磷酸腺苷(cAMP)、蛋白激酶A(PKA)、环磷酸腺苷反应元件结合蛋白(CREB)、磷酸化CREB(p-CREB)、B淋巴细胞瘤-2(Bcl-2)和Bcl-2相关x蛋白(Bax)的表达，并计算p-CREB/CREB比值和Bcl-2/Bax比值。n 结果:与S组比较，I/R组血清CK-MB和LDH水平升高，心肌梗死体积百分比升高，心肌组织GLP-1R表达上调，cAMP和PKA表达下调，p-CREB/CREB比值和Bcl-2/Bax比值降低(n P<0.05)；与I/R组比较，ISP组血清CK-MB和LDH水平降低，心肌梗死体积百分比降低，心肌组织GLP-1R、cAMP和PKA表达上调，p-CREB/CREB比值和Bcl-2/Bax比值升高(n P<0.05)；与ISP组比较，ISPE组血清CK-MB和LDH水平升高，心肌梗死体积百分比升高，心肌组织GLP-1R、cAMP和PKA表达下调，p-CREB/CREB比值和Bcl-2/Bax比值降低(n P<0.05)。n 结论:七氟烷后处理可通过激活GLP-1R信号通路，抑制心肌细胞凋亡，减轻大鼠心肌缺血再灌注损伤。“,”Objective:To evaluate the role of glucagon-like peptide-1 receptor (GLP-1R) signaling pathway in sevoflurane postconditioning-induced attenuation of myocardial ischemia-reperfusion (I/R) injury in rats.Methods:Eighty SPF healthy adult male Sprague-Dawley rats, aged 8-10 weeks, weighing 300-340 g, were divided into 4 groups (n n=20 each) by a random number table method: sham operation group (group S), myocardial I/R group (group I/R), myocardial I/R plus sevoflurane postconditioning group (group ISP), and myocardial I/R plus sevoflurane postconditioning plus GLP-1R antagonist group (group ISPE). The myocardial I/R injury model was developed by ligating the left anterior descending branch of the coronary artery for 40 min followed by 2-h reperfusion in anesthetized rats.In group ISP, the rats inhaled 2.4% sevoflurane for 15 min starting from the beginning of reperfusion.In group ISPE, GLP-1R antagonist Exendin9-39 50 μg/kg (in 1 ml 0.9% normal saline) was intraperitoneally injected once a day from 28 days before development of the model, the last intraperitoneal injection was completed at 40 min before inhalation of sevoflurane, and the other treatments were the same as those previously described in group ISP.Blood samples from the abdominal aorta were collected immediately after reperfusion to determine the serum levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). Then the rats were sacrificed, and the hearts were obtained for microscopic examination of the histopathological changes of myocardial tissues (by HE staining) and the ultrastructure of cardiomyocytes (with a transmission electron microscope) for determination of the myocardial infarct size (TTC staining), expression of GLP-1R in myocardium (by immunohistochemical staining), expression of GLP-1R, cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element-binding protein (CREB), phospho-CREB (p-CREB), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated x protein (Bax) in myocardium (by Western blot). The ratios of p-CREB/CREB and Bcl-2/Bax were calculated.n Results:Compared with group S, the serum levels of CK-MB and LDH and percentage of myocardial infarct size were significantly increased, the expression of GLP-1R was up-regulated, the expression of cAMP and PKA was down-regulated, and the p-CREB/CREB ratio and Bcl-2/Bax ratio were decreased in group I/R (n P<0.05). Compared with group I/R, the serum levels of CK-MB and LDH and percentage of myocardial infarct size were significantly decreased, the expression of GLP-1R, cAMP and PKA was up-regulated, and p-CREB/CREB ratio and Bcl-2/Bax ratio were increased in group ISP (n P<0.05). Compared with group ISP, the serum levels of CK-MB and LDH and percentage of myocardial infarct size were significantly increased, the expression of GLP-1R, cAMP and PKA was down-regulated, and the p-CREB/CREB ratio and Bcl-2/Bax ratio were decreased in group ISPE (n P<0.05).n Conclusions:Sevoflurane postconditioning can attenuate myocardial I/R injury by activation of GLP-1R signal pathway and inhibition of cardiomyocyte apoptosis in rats.