CAJ | 학술논문

目的评价线粒体融合蛋白-2(Mfn-2)表达与糖尿病因素影响大鼠七氟醚后处理心肌保护作用的关系.方法健康雄性SD大鼠,体重210～260 g,腹腔注射链脲佐菌素60 mg/kg制备糖尿病模型.取糖尿病模型制备成功的大鼠36只,采用随机数字表法分为3组(n-12):假手术组(DMS组)、心肌缺血再灌注组(DMIR组)和七氟醚后处理组(DMSP组).另取正常SD大鼠36只,采用随机数字表法分为3组(n=12):假手术组(NS组)、缺血再灌注组(NIR组)和七氟醚后处理组(NSP组).采用结扎左冠状动脉前降支30 min,再灌注120 min的方法制备大鼠心肌缺血再灌注损伤模型;NSP组和DMSP组于再灌注前1 min时吸人七氟醚行后处理,呼气末浓度2.5％,持续5 min.再灌注120 min时处死大鼠,取心肌组织,测定心肌梗死体积、细胞凋亡指数和Mfn-2表达,光镜下观察病理学结果,电镜下观察心肌细胞线粒体超微结构.结果与NS组比较,NIR组和NSP组心肌梗死体积增大,细胞凋亡指数升高,心肌组织Mfn-2表达下调(P＜0.05);与NIR组比较,NSP组心肌梗死体积减小,细胞凋亡指数降低,心肌组织Mfn-2表达上调,DMIR组心肌梗死体积增大,细胞凋亡指数升高,心肌组织Mfn-2表达下调(P＜0.05);与DMS组比较,DMIR组和DMSP组心肌梗死体积增大,细胞凋亡指数升高,心肌组织Mfn-2表达下调(P＜0.05);与DMIR组比较,DMSP组心肌梗死体积、细胞凋亡指数和心肌组织Mfn-2表达差异无统计学意义(P＞0.05);与NSP组比较,DMSP组心肌梗死体积增大,细胞凋亡指数升高,心肌组织Mfn-2表达下调(P＜0.05).NSP组病理学损伤较NIR组减轻.DMSP组病理学损伤较DMIR组未见减轻.结论糖尿病因素取消大鼠七氟醚后处理心肌保护作用的机制可能与抑制Mfn-2表达上调有关.
목적 평개선립체융합단백-2(Mfn-2)표체여당뇨병인소영향대서칠불미후처리심기보호작용적관계.방법 건강웅성SD대서,체중210～260 g,복강주사련뇨좌균소60 mg/kg제비당뇨병모형.취당뇨병모형제비성공적대서36지,채용수궤수자표법분위3조(n-12):가수술조(DMS조)、심기결혈재관주조(DMIR조)화칠불미후처리조(DMSP조).령취정상SD대서36지,채용수궤수자표법분위3조(n=12):가수술조(NS조)、결혈재관주조(NIR조)화칠불미후처리조(NSP조).채용결찰좌관상동맥전강지30 min,재관주120 min적방법제비대서심기결혈재관주손상모형;NSP조화DMSP조우재관주전1 min시흡인칠불미행후처리,호기말농도2.5％,지속5 min.재관주120 min시처사대서,취심기조직,측정심기경사체적、세포조망지수화Mfn-2표체,광경하관찰병이학결과,전경하관찰심기세포선립체초미결구.결과 여NS조비교,NIR조화NSP조심기경사체적증대,세포조망지수승고,심기조직Mfn-2표체하조(P＜0.05);여NIR조비교,NSP조심기경사체적감소,세포조망지수강저,심기조직Mfn-2표체상조,DMIR조심기경사체적증대,세포조망지수승고,심기조직Mfn-2표체하조(P＜0.05);여DMS조비교,DMIR조화DMSP조심기경사체적증대,세포조망지수승고,심기조직Mfn-2표체하조(P＜0.05);여DMIR조비교,DMSP조심기경사체적、세포조망지수화심기조직Mfn-2표체차이무통계학의의(P＞0.05);여NSP조비교,DMSP조심기경사체적증대,세포조망지수승고,심기조직Mfn-2표체하조(P＜0.05).NSP조병이학손상교NIR조감경.DMSP조병이학손상교DMIR조미견감경.결론 당뇨병인소취소대서칠불미후처리심기보호작용적궤제가능여억제Mfn-2표체상조유관.
Objective To evaluate the relationship between mitofusin-2 (Mfn-2) expression and diabetes mellitus (DM)-caused influence on cardioprotection induced by sevoflurane postconditioning in rats.Methods Healthy male Sprague-Dawley rats, weighing 210-260 g, were studied.DM was induced by intraperitoneal 1％ streptozotocin 60 mg/kg, and confirmed by blood glucose ≥ 16.7 mmol/L 72 h later.Thirty-six rats with DM were randomly divided into 3 groups (n =12 each) using a random number table:sham operation group (group DMS) , myocardial ischemia-reperfusion group (group DMIR) , and sevoflurane postconditioning group (group DMSP).Another 36 normal rats were selected, and were also randomly divided into 3 groups (n=12 each) using a random number table: sham operation group (group NS) , myocardial ischemia-reperfusion group (group NIR) , and sevoflurane postconditioniug group (group NSP).Myocardial ischemia was induced by 30 min occlusion of the left anterior descending branch of the coronary artery, followed by 120 min reperfusion.In NSP and DMSP groups, sevoflurane was inhaled for 5 min after the end-tidal concentration reached 2.5％ starting from 1 min before reperfusion.The rats were sacrificed at 120 min of reperfusion, and their hearts were removed for measurement of myocardial infarct size (IS) (by TTC) , cell apoptosis and Mfn2 expression, and for examination of pathological changes (with light microscope) and ultra-structure (with electron microscope).Apoptosis index (AI) was calculated.Results Compared with group NS, the myocardial 1S was significantly enlarged, AI was increased, and the expression of Mfn-2 was down-regulated in NIR and NSP groups (P＜0.05).Compared with group NIR, the myocardial IS and AI were significantly decreased, and the expression of Mfn-2 was up-regulated in group NSP,and the myocardial IS was enlarged, AI was increased, and the expression of Mfn-2 was down-regulated in group DMIR (P＜0.05).Compared with group DMS, the myocardial IS was significantly enlarged, AI was increased, and the expression of Mfn-2 was down-regulated in DMIR and DMSP groups (P＜0.05).Compared with group DMIR, no significant change was found in the myocardial IS, AI and Mfn-2 expression in group DMSP (P＞0.05).Compared with group NSP, the myocardial IS was significantly enlarged, AI was increased, and the expression of Mfn-2 was down-regulated in group DMSR (P＜0.05).The pathological changes were significantly attenuated in group NSP compared with group NIR.No significant difference was found in pathological changes between group DMSP and group DMIR.Conclusion The mechanism by which DM abolishes cardioprotection induced by sevoflurane postconditioning may be related to inhibited upregulation of Mfn-2 expression in rats.