摘要
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.
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.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2014年第7期883-885,共3页
Chinese Journal of Anesthesiology
