摘要
目的评价NF-kB信号通路和自噬在吸入七氟烷大鼠延迟性心肌保护中的作用。方法成年雄性SD大鼠96只，体重270～350g，采用随机数字表法，将大鼠随机分为6组（n=16）：假手术组（S组）；缺血再灌注组（I／R组）吸入33％氧气2h；七氟烷组（SEVO组）吸入2．5％七氟烷2h；NF-kB特异性抑制剂FIN组（PTN组）和二甲基亚砜组（DMSO组）分别于吸入氧气前15min腹腔注射PTN500μg/kg和DMSO；PTN＋七氟烷组（PTN＋SEVO组）于吸人七氟烷前15min腹腔注射mN500μg／kg，24h后制备大鼠心肌缺血再灌注模型。于缺血前即刻随机取8只大鼠处死取心脏，采用EMSA法检测心肌NF-kB活性，Westernblot法检测自噬相关蛋白LC3-Ⅱ和cathepsinB的表达。于再灌注2h时各组余大鼠处死取心脏，采用TIC染色法测定心肌梗死范围。结果与s组比较，其余组再灌注2h时大鼠心肌梗死范围增加，SEVO组大鼠缺血前即刻心肌NF-kB、LC3-Ⅱ和cathepsinB水平升高（P〈0．05）；与I／R组比较，SEVO组大鼠缺血前即刻心肌NF-kB、LC3-Ⅱ和cathepsinB水平升高，再灌注2h时大鼠心肌梗死范围减小（P〈0．05）；与SEVO组比较，DMSO组、PTN组和PTN＋SEVO组大鼠缺血前即刻心肌NF—kB、LC3-Ⅱ和cathepsinB水平降低，再灌注2h时大鼠心肌梗死范围增加（P〈0．05）。结论NF-kB信号通路和自噬参与了吸入七氟烷大鼠产生延迟性心肌保护作用的过程。
Objective To evaluate nuclear factor （NF）-kB signaling pathway and autophagy in inhaled sevoflurane-produced delayed myocardial protection in rats. Methods Ninety-six adult male Sprague-Dawley rats, weighing 270-350 g, were randomly assigned into 6 groups （ n = 16 each） ： sham operation group （group S）, isch- emia-reperfusion （I/R） group, sevoflurane group （SEVO group）, specific NF-kB inhibitor parthenolide （PTN） group, dimethyl sulfoxide （DMSO） group and PTN ＋ sevoflurane group （ PTN ＋ SEVO group）. The animals were anesthetized with intraperitoneal pentobarbital 50 mg/kg, intubated and mechanically ventilated. Myocardial I/R was induced by 30 min of occlusion of the left anterior descending branch of coronary artery followed by 2 h of reperfusion. In group I/RI 33% oxygen was inhaled for 2 h. In group SEVO, 2.5% sevoflurane was inhaled for 2 h. In groups PTN and DMSO, PTN 500 μg/kg and DMSO were administered intraperitoneally 15 min before oxy- gen inhalation respectively. In group PTN ＋ SEVO, PTN 500 ttg/kg was administered intaperitoneally 15 min be- fore exposure to sevoflurane. Myocardial I/R was induced 24 h after intraperitoneal administration. Eight animals in each group were sacrificed immediately before ischemia and the hearts were removed to detect the NF-kB activity and expression of LC3-Ⅱ and cathepsin B. The left animals in each group were sacrificed at 2 h of reperfusion and the hearts were removed to determine the myocardial infarct size （by TTC staining）. Results Compared with group S, the myocardial infarct size was significantly increased at 2 h of reperfusion in the other groups, and the NF-kB activity was significantly increased and the expression of LC3-Ⅱ and cathepsin B was up-regulated immediately be- fore ischemia in group SEVO （P 〈 0.05）. Compared with group I/R, the NF-kB activity was significantly in- creased and the expression of LC3-Ⅱ and cathepsin B was up-regulated immediately before ischemia, and the myo- cardial infarct siz
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2012年第8期995-998,共4页
Chinese Journal of Anesthesiology
基金
江苏省“科教兴卫工程”
苏州市科技发展计划项目（SYS201038,SYS201130）
苏州大学附属第二医院青年科研基金（SDFEYQN1107,SDFEYQN1108）
关键词
麻醉药
吸入
心肌再灌注损伤
NF-KB
Anesthetic, inhalation
Myocardial reperfusion injury
NF-kappa B
