CAJ | 학술논문

目的评价核因子E2相关因子-2(Nrf2)/抗氧化反应元件(ARE)信号通路在异丙酚减轻大鼠心肌缺血再灌注损伤中的作用.方法雄性成年SD大鼠60只,体重200～ 240 g,采用随机数字表,将其分为5组(n=12):假手术组(S组)、缺血再灌注组(I/R组)、异丙酚组(P组)、异丙酚+Nrf2空白质粒组(PNV组)和异丙酚+Nrf2-siRNA质粒组(PNS组).吸入2％异氟醚麻醉后,气管插管行机械通气.采用结扎冠状动脉左前降支5 min,再灌注60 min的方法制备大鼠心肌缺血再灌注损伤模型.P组、PNV组和PNS组气管插管成功后停止吸入异氟醚,尾静脉输注异丙酚6 mg·kg-1·h至再灌注30min;输注异丙酚30 min时PNV组心肌内注射Nrf2空质粒液10μg (100 μl),PNS组心肌内注射Nrf2-siRNA质粒混悬液10 μg(100μl),然后制备大鼠心肌缺血再灌注损伤模型.再灌注60 min时处死大鼠,取心肌组织,测定心肌细胞凋亡指数、心肌梗死体积、Nrf2和血红素氧合酶-1(HO-1)的表达.结果与S组比较,I/R组和P组心肌梗死体积和心肌细胞凋亡指数升高,心肌组织Nrf2和HO-1的表达上调(P＜0.05);与I/R组比较,P组心肌梗死体积和心肌细胞凋亡指数降低,心肌组织Nrf2和HO-1的表达上调(P＜0.05);与P组比较,PNV组心肌梗死体积、心肌细胞凋亡指数、心肌组织Nrf2和HO-1的表达差异无统计学意义(P＞0.05),PNS组心肌梗死体积和心肌细胞凋亡指数升高,心肌组织Nrf2和HO-1的表达下调(P＜0.05).结论 Nrf2/ARE信号通路参与了异丙酚减轻大鼠心肌缺血再灌注损伤.
목적 평개핵인자E2상관인자-2(Nrf2)/항양화반응원건(ARE)신호통로재이병분감경대서심기결혈재관주손상중적작용.방법 웅성성년SD대서60지,체중200～ 240 g,채용수궤수자표,장기분위5조(n=12):가수술조(S조)、결혈재관주조(I/R조)、이병분조(P조)、이병분+Nrf2공백질립조(PNV조)화이병분+Nrf2-siRNA질립조(PNS조).흡입2％이불미마취후,기관삽관행궤계통기.채용결찰관상동맥좌전강지5 min,재관주60 min적방법제비대서심기결혈재관주손상모형.P조、PNV조화PNS조기관삽관성공후정지흡입이불미,미정맥수주이병분6 mg·kg-1·h지재관주30min;수주이병분30 min시PNV조심기내주사Nrf2공질립액10μg (100 μl),PNS조심기내주사Nrf2-siRNA질립혼현액10 μg(100μl),연후제비대서심기결혈재관주손상모형.재관주60 min시처사대서,취심기조직,측정심기세포조망지수、심기경사체적、Nrf2화혈홍소양합매-1(HO-1)적표체.결과 여S조비교,I/R조화P조심기경사체적화심기세포조망지수승고,심기조직Nrf2화HO-1적표체상조(P＜0.05);여I/R조비교,P조심기경사체적화심기세포조망지수강저,심기조직Nrf2화HO-1적표체상조(P＜0.05);여P조비교,PNV조심기경사체적、심기세포조망지수、심기조직Nrf2화HO-1적표체차이무통계학의의(P＞0.05),PNS조심기경사체적화심기세포조망지수승고,심기조직Nrf2화HO-1적표체하조(P＜0.05).결론 Nrf2/ARE신호통로삼여료이병분감경대서심기결혈재관주손상.
Objective To evaluate the role of nuclear factor erythroid 2-related factor 2/antioxidant responsive element (Nrt2/ARE) signaling pathway inthe reduction of myocardial ischemia-reperfusion (I/R) injury by propofol in rats.Methods Sixty adult male Sprague-Dawley rats,weighing 200-240 g,were randomly divided into 5 groups (n =12 each) using a random number table:sham operation group (S group),I/R group,propofol group (P group),propofol + Nrf2 vehicle-plasmid group (PNV group) and propofol + Nrf2 siRNA plasmid group (PNS group).The animals were anesthetized with inhalation of 2％ isoflurane,tracheally intubated and mechanically ventilated.Myocardial I/R was produced by 5 min occlusion of left anterior descending branch of coronary artery followed by 60 min reperfusion.In P,PNV and PNS groups,isoflurane inhalation was stopped after successful intubation and propofol was infused via the caudal vein at 6 mg· kg-1 · h-1 until 30 of reperfusion.At 30 min of propofol infusion,Nrf2 vehicle-plasmid 10 μg (100 μl) was injected intramyocardially before myocardial ischemia in group PNV,and Nrf2 siRNA 10 μg (100 μl) was injected intramyocardially before myocardial ischemia in group PNS.The animals were sacrificed at 60 min of reperfusion and myocardial specimens were taken for determination of the infarct size,apoptosis index,and the expression of Nrf2 and heme oxygenase-1 (HO-1).Results Compared with group S,the infarct size and apoptosis index were significantly increased,and the expression of Nrf2 and HO-1 was up-regulated in I/R and P groups.Compared with group I/R,the infarct size and apoptosis index were significantly decreased,and the expression of Nrf2 and HO-1 was up-regulated in group P.Compared with group P,no significant changes were found in the infarct size,apoptosis index and expression of Nrf2 and HO-1 in group PNV,and the infarct size and apoptosis index were significantly increased,and the expression of Nrf2 and HO-1 was down-regulated in group PNS.Conclusion Nrf2/ARE signaling pathway is involved in the reduction of myocardial I/R injury by propofol in rats.